Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP100 and TRP2 , two melanoma-derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH modification on the inner hollow core and COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8 and CD4 T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.

BackgroundFor cases of severe traumatic brain injury, during primary operation, neurosurgeons usually face a dilemma of whether or not to remove the bone flap after mass lesion evacuation. Decompressive craniectomy, which involves expansion of fixed cranial cavity, is used to treat intra-operative brain swelling and post-operative malignant intracranial hypertension. However, due to indefinite indication, the decision to perform this procedure heavily relies on personal experiences. In addition, decompressive craniectomy is associated with various complications, and the procedure lacks strong evidence of better outcomes. In the present study, we designed a prospective, randomized, controlled trial to clarify the effect of decompressive craniectomy in severe traumatic brain injury patients with mass lesions.MethodsPRECIS is a prospective, randomized, assessor-blind, single center clinical trial. In this trial, 336 patients with traumatic mass lesions will be randomly allocated to a therapeutic decompressive craniectomy group or a prophylactic decompressive craniectomy group. In the therapeutic decompressive craniectomy group, the bone flap will be removed or replaced depending on the emergence of brain swelling. In the prophylactic decompressive craniectomy group, the bone flap will be removed after mass lesion evacuation. A stepwise management of intracranial pressure will be provided according to the Brain Trauma Foundation guidelines. Salvage decompressive craniectomy will be performed for craniotomy patients once there is evidence of imaging deterioration and post-operative malignant intracranial hypertension. Participants will be assessed at 1, 6 and 12 months after randomization. The primary endpoint is favorable outcome according to the Extended Glasgow Outcome Score (5–8) at 12 months. The secondary endpoints include quality of life measured by EQ-5D, mortality, complications, intracranial pressure and cerebral perfusion pressure control and incidence of salvage craniectomy in craniotomy patients at each investigation time point.DiscussionThis study will provide evidence to optimize primary decompressive craniectomy application and assess outcomes and risks for mass lesions in severe traumatic brain injury.Trial registrationISRCTN20139421

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BackgroundSpinal cord injuries (SCIs) are sustained by an increasing number of patients each year worldwide. The treatment of SCIs has long been a hard nut to crack for doctors around the world. Mesenchymal stem cells (MSCs) have shown benefits for the repair of SCI and recovery of function. Our present study aims to investigate the effects of intravenously infused human umbilical cord blood-derived MSCs (hUCB-MSCs) on functional recovery after subacute spinal cord compression injury of two noncontinuous segments. In addition, we compared the effects of single infusion and repeated intravenous (i.v.) injections on the recovery of spinal cord function.MethodsA total of 43 adult rabbits were randomly divided into four groups: control, single injection (SI), repeated injection at a 3-day (3RI) or repeated injection at a 7-day interval (7RI) groups. Non-immunosuppressed rabbits in the transplantation groups were infused with either a single complete dose or three divided doses of 2 × 106 hUCB-MSCs (3-day or 7-day intervals) on the first day post decompression. Behavioural scores and somatosensory evoked potentials (SEPs) were used to evaluate hindlimb functional recovery. The survival and differentiation of the transplanted human cells and the activation of the host glial and inflammatory reaction in the injured spinal cord were studied by immunohistochemical staining.ResultsOur results showed that hUCB-MSCs survived, proliferated, and primarily differentiated into oligodendrocytes in the injured area. Treatment with hUCB-MSCs reduced the extent of astrocytic activation, increased axonal preservation, potentially promoted axonal regeneration, decreased the number of Iba-1+ and TUNEL+ cells, increased the amplitude and decreased the onset latency of SEPs and significantly promoted functional improvement. However, these effects were more pronounced in the 3RI group compared with the SI and 7RI groups.ConclusionsOur results suggest that treatment with i.v. injected hUCB-MSCs after subacute spinal cord compression injury of two noncontinuous segments can promote functional recovery through the differentiation of hUCB-MSCs into specific cell types and the enhancement of anti-inflammatory, anti-astrogliosis, anti-apoptotic and axonal preservation effects. Furthermore, the recovery was more pronounced in the rabbits repeatedly injected with cells at 3-day intervals. The results of this study may provide a novel and useful treatment strategy for the transplantation treatment of SCI.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0879-0) contains supplementary material, which is available to authorized users.

ICP monitor placement was associated with a significant decrease in 6-month mortality after adjustment for the baseline risk profile and the monitoring propensity of patients with diffuse severe TBI, especially those with GCS scores of 3 to 5 or of Marshall computed tomography classification IV.