A laponite-based immunologically active gel delivery system for long-acting tumor vaccine.

Traditional bolus vaccines typically require multiple doses, which complicates the vaccination process and may cause missed shots, leading to sub-optimal immunity and reduced vaccine effectiveness. Herein, a gel-based long-acting vaccine system with self-adjuvant properties based on laponite was constructed to simplify vaccination procedures and improve vaccine effectiveness. Firstly, the gel system could recruit multiple types of immune cells to form immune niches. Secondly, it could achieve sustained delivery of antigens to lymph nodes by active transport and passive drainage. Then, the gel system triggered the formation of a large number of germinal centers, which elicited enhanced and durable humoral immune responses, as well as strong cellular immune responses. As a result, it eventually showed good prophylactic and therapeutic effects in a variety of tumor models including melanoma, colorectal cancer and peritoneal metastasis models. By further combining the immunoadjuvant CpG ODN and cytokine IL-12, the effect of the gel-vaccine could be further enhanced. In a murine peritoneal metastasis model of colorectal carcinoma, a single administration of the gel-vaccine resulted in complete tumor eradication in 8/9 mice. In summary, this study developed an immunologically active gel-vaccine system. And as a robust and versatile vaccine platform, by loading different antigens and adjuvants, this gel-vaccine system is expected to realize its better therapeutic potential.

Hybrid biomineralized nanovesicles to enhance inflamed lung biodistribution and reduce side effect of glucocorticoid for ARDS therapy.

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs.

Anatomy of the Plantar Intermetatarsal Tunnel: A Cadaveric Study.

The contents of the plantar intermetatarsal tunnel (PIMT) and the relationship between the common plantar interdigital nerve (CPIN) and the PIMT were recorded. The width of the PIMT was measured at the metatarsal neck (MTN), metatarsophalangeal (MTP) joint and the base of the proximal phalanx (BPP). The length of the deep transverse metatarsal ligament (DTML), the PIMT and the intracapsular ligament (ICL) were also measured. The PIMT was revealed to be a narrow osseofibrous tunnel divided into 3 segments by the DTML: the distal section, the area under the DTML (middle) and the proximal section. The length of the middle section was 12.77 mm in the second intermetatarsal (IM) space and 10.18 mm in the third IM space. The lengths of the distal sections were 15.52 and 14.95 mm in the second and third IM spaces, respectively. There was some soft tissue between the CPIN and PIMT, and the CPIN was observed not to glide freely within the tunnel. The widths of the PIMT at the MTN, MTP joint and BPP were respectively 2.87, 2.56, and 3.42 mm in the second IM space and 3.10, 2.68 and 3.61 mm in the third IM space. The ICL lies between the capsules of the MTP joint, and the length of the ICL was 2.76 and 3.03 mm in the second and third IM spaces, respectively. The PIMT was found to be a complex spatial structure, and the ICL might prevent the CPIN from being squeezed into the IM space.

Serum levels of 25-hydroxyvitamin D and functional outcome among postmenopausal women with hip fracture.

OBJECTIVE: The main objective of the current study was to assess the distribution and its prognostic value of serum 25-hydroxyvitamin D (25[OH] D) levels assessed at admission in Chinese postmenopausal women with hip fracture. METHODS: From January 1, 2012 to December 31, 2013, all postmenopausal women with first-ever hip fracture were recruited to participate in the study. Serum 25[OH] D levels were measured at admission. The functional evaluation at the time of discharge was performed by the Barthel Index (BI). The prognostic value of 25[OH] D to predict the functional outcome within discharge was analyzed by logistic regression analysis, after adjusting for the possible confounders. RESULTS: In our study, 261 patients were included and assessed. In the 76 patients with an unfavorable functional outcome, serum 25(OH) D levels were lower compared with those in patients with a favorable outcome [11.8(IQR, 9.9-16.1) ng/ml; 16.8(IQR, 13.6-21.4) ng/ml, respectively; P<0.0001]. In multivariate analysis, there was an increased risk of unfavorable outcome associated with serum 25(OH) D levels ≤ 20 ng/ml (OR 5.24, 95%CI: 3.11-8.15; P<0.0001) after adjusting for possible confounders. CONCLUSIONS: Our data support an association between serum 25[OH] D levels and prognosis in Chinese postmenopausal women with hip fracture.