Public long-term care insurance and consumption of elderly households: Evidence from China.

This study investigates the impact of long-term care insurance (LTCI) on the non-health consumption of elderly households. By exploiting a quasi-experiment on the public LTCI pilot program in China, we identify the effect of LTCI using a triple-difference approach. Using longitudinal data from the China Health and Retirement Longitudinal Study, we find that LTCI has led to an increase in the non-health consumption of elderly households by 15.7%, mostly observed in households having no older members with need for long-term care (LTC). Further evidence suggests that the effects are stronger for households with higher expected LTC risks, less wealth or family insurance, and covered by more generous schemes. Finally, LTCI increases the expectation of using formal LTC when disabled and subjective longevity expectations for older adults having no need for LTC. Overall, these findings offer empirical support for the role of LTCI in mitigating precautionary savings against LTC risks.

Nasal Caffeine Thermo-Sensitive In Situ Gel for Enhanced Cognition after Sleep-Deprivation.

BACKGROUND: Caffeine abundant in coffee has a strong excitation effect on the central nerve system (CNS). METHODS: To combat the adverse effects of sleep deprivation on physical and mental health, this article designed a new nasal temperature-sensitive gel loaded with caffeine, whose effects of awakening and improving cognition in sleep-deprived rats were evaluated. RESULTS: It was found that the caffeine thermo-sensitive in situ gel (TSG) stayed in the nasal cavity for a longer time and increased the contact time between the drugs and the nasal mucosa, which made it possible for caffeine TSG to exert a lasting effect. Secondly, compared with sleep-deprived rats, those administrated with caffeine TSG were more responsive in behavioral experiments. Moreover, the antipentobarbital test proved that caffeine TSG could prolong the sleep latency and shorten the sleep time. Furthermore, caffeine TSG could significantly restore the cognitive ability by ameliorating neuronal cell injuries by upregulating brain-derived neurotrophic factor (BDNF) levels. CONCLUSION: Generally, caffeine TSG could quickly exert the efficacy of enhancing cognition and wakefulness, and overcome the drawbacks of frequent medications. It can potentially be used for the treatment of psychiatric disorders, such as dementia, Parkinson and Alzheimer's disease.

Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-α caused by PTSD. Western blot analysis showed that CBD TSGs increased the expression of the 5-HT1A receptor. Intranasal administration of CBD TSGs was more efficient and had more obvious brain targeting effects than oral administration, as evidenced by the pharmacokinetics and brain tissue distribution of CBD TSGs. Overall, nasal CBD TSGs are safe and effective and have controlled release. There are a novel promising option for the clinical treatment of PTSD.

Effects of armodafinil nanocrystal nasal hydrogel on recovery of cognitive function in sleep-deprived rats.

Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for > 4 h and then penetrating the mucosa as quickly as possible in vitro. We found that armodafinil NCsG was biologically safe, as it had no visible ciliary toxicity, as well as extremely stable due to the existence of intermolecular hydrogen-bonding forces. Nasal administration of armodafinil NCsG proved to be more efficient and targeted than oral administration due to its preferential absorption in plasma and more-concentrated distribution in the brain. In addition, compared with the model group, sleep-deprived rats treated with NCsG undergoing Morris water maze (MWM) behavioral experiments had shorter escape latency and much more shuttle times across the platform. Meanwhile, in the open-field test (OFT), these same rats had longer periods of movement in the center, longer time spent upright, and lower anxiety, which clearly demonstrated improved cognitive awareness and wakefulness after intranasal administration. Moreover, we speculated that armodafinil NCsG had a protective effect on hippocampal neurons in Cortical Area 1 (CA1), which is closely related to cognitive function, by upregulating brain-derived neurotrophic factor (BDNF) protein expression. Consequently, the intranasal administration of armodafinil NCsG could serve as a promising integrated-control measure for sleep deprivation.

3D printing-based drug-loaded implanted prosthesis to prevent breast cancer recurrence post-conserving surgery.

Systemic chemotherapy of breast cancer is commonly delivered as a large dose and has toxic side effects. Local chemotherapy would overcome the shortcomings of systemic reconstruction and could play an important role in breast cancer surgery according to personalized demand. The application of three-dimensional (3D) printing technology makes personalized customization possible. We designed and prepared a prosthesis containing paclitaxel (PTX) and doxorubicin (DOX) microspheres (PPDM) based on 3D printing to prevent tumor recurrence and metastasis after breast conserving surgery. Polydimethysiloxane has good biocompatibility and was used as a drug carrier in this study. The average particle size of the PTX and DOX microspheres were approximately 3.1 µm and 2.2 µm, respectively. The drug loading of PTX and DOX microspheres was 4.2% and 2.1%, respectively. In vitro drug release studies demonstrated that the 3D-printed prosthesis loaded with PTX and DOX microspheres could release the drugs continuously for more than 3 weeks and thereby suppress cancer recurrence with reduced side effects. The PTX and DOX microspheres not only exerted a synergistic effect, but also achieved a good sustained release effect. In vivo evaluation showed that the PPDM could effectively inhibit breast cancer recurrence and metastasis in mice with breast cancer. PPDM are expected to achieve postoperative chemotherapy for breast cancer and be highly efficient to prevent local breast cancer recurrence and metastasis.

Comparative study of oral and intranasal puerarin for prevention of brain injury induced by acute high-altitude hypoxia.

Human activities in the areas of high altitude have increased significantly recently. Brain is highly sensitive to changing of oxygen pressure due to high altitude, and this physiological response may lead to serious brain injury, such as learning and memory disabilities. Puerarin is a phytoestrogen with many pharmacological activities, such as treatment of neurological disorders. However, most of current drugs can not easily enter brain through the blood-brain barrier (BBB). The nose-to-brain route can bypass BBB for brain-targeting. Here, thermosensitive in situ hydrogels (TISGs) of puerarin were prepared with poloxamers 407, poloxamers 188 and propylene glycol to improve bioavailability and brain targeting. In vitro drug release in simulated nasal fluids, rheological properties and cilia toxicity of puerarin TISGs were explored. The pharmacodynamics and pharmacokinetics of puerarin by intranasal (i.n.) and oral (p.o.) administrations were also evaluated. The viscosity of puerarin TISGs tended to increase obviously with increased temperature. The puerarin release profile and transmucosal process of puerarin TISGs could be described with the first-order kinetics equation, depending on drug diffusion. The cilia toxicity of puerarin TISGs was not obvious. Rat models of hypobarism/hypoxia-induced brain injury were established with a hypobaric simulation chamber. Morris water maze and open filed tests indicated that puerarin TISGs improved the spatial memory and spontaneous exploratory behavior of the rats suffering from hypoxia-induced brain injury. Furthermore, puerarin TISGs decreased the level of oxidative stress cytokines (malondialdehyde (MDA) and glutathione (GSH)) in the peripheral circulation, alleviated the cerebral histological lesions, and relieved the expression of hypoxia-inducible factor-1α (HIF-1α). Intranasal puerarin TISGs were absorbed quickly with a shorter Tmax (10.0 ± 5.7 min) compared to that of oral puerarin (36 ± 13.4 min). In addition, the relative bioavailability of i.n. puerarin TISGs was high to 300% compared to oral administration of puerarin. The area under the curve (AUC) of brain after i.n. administration of puerarin TISGs was 954.5 ± 335.1 h.ng/mL, while no puerarin was detected in the brain after oral administration. Therefore, i.n. puerarin TISGs led to excellent brain targeting effect. Puerarin TISGs are an effective neuroprotector formulation for prevention of brain injury induced by acute high-altitude hypoxia.

Topical photodynamic therapy combined with ablative "light needles" against basal cell carcinoma.

Basal cell carcinoma (BCC), a non-melanoma cancer with high morbidity in the elders, is a type of limited skin cancer with a projected appearance. Traditional treatments such as oral or injection administration are likely to result in serious side effects. Here, we developed a strategy that combined photodynamic therapy (PDT) with ablative light "needles" (carbon-dioxide laser) for the treatment of BCC, involving ß-Tetra-(4-carboxyl-phenoxy)-zinc phthalocyanine (ZnPC4) cubic phases with high drug loading, easy preparation, long local retention, good spreading ability and little toxicity. A model of nude mice with BCC was established for the study of pharmacodynamics. The light needles of low energy (53 mJ/cm2) used here could promote transdermal absorption of ZnPC4 cubic phases while those of high energy (238 mJ/cm2) alone could completely kill tumor cells with no recurrence. However, ZnPC4 cubic phases alone could not completely inhibit tumor growth, for it was distributed mainly at the topical administration site in the absence of any adjuvant technology. Therefore, the combination of photodynamics and light needles offered a good solution. Especially, the combined use of light needles with high energy and ZnPC4 cubic phases can treat BCC efficiently with no recurrence. This approach is expected to be a novel and promising medication against BCC.

ICG-loaded photodynamic chitosan/polyvinyl alcohol composite nanofibers: Anti-resistant bacterial effect and improved healing of infected wounds.

Photodynamic antimicrobial chemotherapy (PACT) has advantages of strong targeting, low resistance to drugs. Electrospinning nanofibers is favorable for wound healing. The combination of PACT and electrospinning nanofibers is appropriate for wound healing, especially infected wound. In our study, indocyanine green (ICG) as photosensitizer had obvious inhibition effects on two antibiotic-resistant bacteria, Methicillin-resistant Staphylococcus aureus (MRSA) and Meropenem-resistant Pseudomonas aeruginosa (MRPA). The optimized electrospinning solution consisted of 2% (w/v) chitosan and 7% (w/v) PVA. The nanofibers observed by scanning electron microscope showed a three-dimensional cross-network with smooth surface, the water absorption ratio of the nanofibers was up to 210%. Fourier transform infrared spectrum and X-ray diffraction showed that the intermolecular hydrogen bonding happened between chitosan and PVA in electrospinning process, which was favorable for the formation of nanofibers. ICG released rapidly from the surface of the nanofibers first and then released continuously. The photodynamic nanofibers could inhibit the bacteria and decreased the F4/80 expression of MRSA-infected rats. The improved effects of wound healing were evaluated with the morphology, wound healing radio, the increased expression of cluster of differentiation 31 (CD31), the decreased level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The photosensitizer-loaded electrospinning nanofibers provide a novel promising option for treatment of infected wound.

Electroporation-enhanced transdermal drug delivery: Effects of logP, pKa, solubility and penetration time.

Electroporation is an important physical technique to improve drug transdermal delivery, although its mechanism remains unclear. Here, some types of polar drugs, including aspirin, diclofenac sodium, metformin hydrochloride, ibuprofen and zidovudine, were used as the model drugs for the exploration of electroporation mechanisms. Electroporation had great influences on the structure of stratum corneum to improve the cumulative permeability due to the formation of pores maintaining for at least 2 h, depending on the power and time, and then the permeation gradually recovered to the normal value after 12 h. A mathematical model was firstly established to exhibit the relationship between the electroporation-improving cumulative permeation and the physiochemical properties of the model drugs, involving oil-water partition coefficient (logP), dissociation constant (pKa) and solubility (S). Increased cumulative permeation depended on increased S, decreased logP and pKa. Electroporation is an effective physical technique to improve transdermal drug delivery depending on itself and the properties of drugs.

Intranasal tetrandrine temperature-sensitive in situ hydrogels for the treatment of microwave-induced brain injury.

The brain is the most sensitive organ to microwave radiation. However, few effective drugs are available for the treatment of microwave-induced brain injury due to the poor drug permeation into the brain. Here, intranasal tetrandrine (TET) temperature-sensitive in situ hydrogels (ISGs) were prepared with poloxamers 407 and 188. Its characteristics were evaluated, including rheological properties, drug release in vitro, and mucosal irritation. The pharmacodynamics and brain-targeting effects were also studied. The highly viscous ISGs remained in the nasal cavity for a long time with the sustained release of TET and no obvious ciliary toxicity. Intranasal temperature-sensitive TET ISGs markedly improved the spatial memory and spontaneous exploratory behavior induced by microwave with the Morris water maze (MWM) and the open field test (OFT) compared to the model. The ISGs alleviated the microwave-induced brain damage and inhibited the certain mRNA expressions of calcium channels in the brain. Intranasal temperature-sensitive TET ISGs was rapidly absorbed with a shorter Tmax (4.8 h) compared to that of oral TET (8.4 h). The brain targeting index of intranasal temperature-sensitive TET ISGs was as 2.26 times as that of the oral TET. Intranasal temperature-sensitive TET ISGs are a promising brain-targeted medication for the treatment of microwave-induced brain injury.

Wound healing of laser injured skin with glycerol monooleicate cubic liquid crystal.

Laser has found increasingly wider applications in the medical filed, but laser is likely to cause damage to patients' skin. In this experiment, we were surprised to find that glyceryl monooleate (GMO)-based cubic liquid crystal had excellent healing effect on the skin of guinea pigs damaged by laser. Transepidermal water loss (TEWL), H.E. pathology, Masson trichrome dyeing, interleukin-6 (IL-6) levels and the percutaneous depth of fluorescein isothiocyanate (FITC) dyeing were used to evaluate the therapeutic effect of GMO-based cubic liquid crystals against laser damage of different degrees among guinea pigs. GMO-based cubic liquid crystals had an obvious effect in the treatment of slight and moderate laser damage. This finding may provide a effective medical treatment protocols for laser skin damage.

Nasal timosaponin BII dually sensitive in situ hydrogels for the prevention of Alzheimer's disease induced by lipopolysaccharides.

Alzheimer's disease (AD) is a common and severe brain disease with a high mortality among the elders, but no highly efficient medications are currently available. For example, timosaponin BII, an efficient anti-AD agent, has low oral bioavailability. Here, timosaponin BII was formulated in a temperature/ion-sensitive in situ hydrogel (ISG) that was well transformed into gels in the nasal environment. Timosaponin BII protected the PC12 cells injured by lipopolysaccharides (LPS) by decreasing TNF-α and IL-1ß and stabilizing F-actin. Timosaponin BII ISGs were intranasally administered to the mice every day for 38 days. On Day 36, LPS was injected to the mice to establish an AD model. Morris water maze experiments showed that the number of the animals that were able to cross the platform returned to normal and the total distance over which the animals moved in the open field also increased, which demonstrated that the spatial memory and spontaneous behavior were improved after treatment compared to the model. Moreover, an AD improver, inducible nitric oxide synthase (iNOS) in the brain, was reduced after treatment. High brain targeting effect of timosaponin BII ISGs was confirmed by in vivo fluorescence imaging. The nasal timosaponin BII dually sensitive ISGs can serve as a promising medication for local prevention of AD.