BackgroundThe safety and immunogenicity of a personalized neoantigen-based peptide vaccine, iNeo-Vac-P01, was reported previously in patients with a variety of cancer types. The current study investigated the synergistic effects of radiofrequency ablation (RFA) and neoantigen vaccination in cancer patients and tumor-bearing mice.MethodsTwenty-eight cancer patients were enrolled in this study, including 10 patients who had received RFA treatment within 6 months before vaccination (Cohort 1), and 18 patients who had not (Cohort 2). Individualized neoantigen peptide vaccines were designed, manufactured, and subcutaneously administrated with GM-CSF as an adjuvant for all patients. Mouse models were employed to validate the synergistic efficacy of combination treatment of RFA and neoantigen vaccination.ResultsLonger median progression free survival (mPFS) and median overall survival (mOS) were observed in patients in Cohort 1 compared to patients in Cohort 2 (4.42 and 20.18 months vs. 2.82 and 10.94 months). The results of ex vivo IFN-γ ELISpot assay showed that patients in Cohort 1 had stronger neoantigen-specific immune responses at baseline and post vaccination. Mice receiving combination treatment of RFA and neoantigen vaccines displayed higher antitumor immune responses than mice receiving single modality. The combination of PD-1 blockage with RFA and neoantigen vaccines further enhanced the antitumor response in mice.ConclusionNeoantigen vaccination after local RFA treatment could improve the clinical and immune response among patients of different cancer types. The synergistic antitumor potentials of these two modalities were also validated in mice, and might be further enhanced by immune checkpoint inhibition. The mechanisms of their synergies require further investigation. Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT03662815.

Objective: To observe the effects of transection of cervical sympathetic trunk (TCST) on the cognitive function of traumatic brain injury (TBI) rats and the potential mechanisms. Methods: A total of 288 adult male SD rats were divided into 3 groups using a random number table: TBI group (n=96), TBI + TCST group (n=96) and Sham group (n=96). The water maze test was performed before TBI (T0) and at day 1 (T 1 ), day 2 (T 2 ), day 3 (T 3 ), 1 week (T 4 ), 2 weeks (T 5 ), 6 weeks (T 6 ) and 12 weeks (T 7 ) after TBI. The levels of α1-adrenergic receptors (α1-ARs), α2-adrenergic receptors (α2-ARs), toll-like receptor 4 (TLR-4) and P38 in hippocampi were detected by real-time PCR. Hippocampal P38 expression was assayed by Western blot. The expressions of interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry. Noradrenaline (NE) expression in plasma was evaluated by ELISA. The respiratory control ratio (RCR) of brain mitochondria was detected using a Clark oxygen electrode. Results: TCST effectively improved the cognitive function of TBI rats. TCST significantly inhibited sympathetic activity in the rats and effectively inhibited inflammatory responses. The expression of BDNF at T 1 -T 6 in TBI+TCST group was higher than that in TBI group ( P <0.05). Furthermore, P38 expression was inhibited more effectively in TBI+TCST group ( P <0.05), than in TBI group ( P <0.05), and the RCR of the brain was significantly higher in TBI+TCST group than in TBI group ( P <0.05). Conclusions: TCST can enhance cognitive function in TBI rats by inhibiting sympathetic activity, reducing inflammatory responses and brain edema, upregulating BDNF and improving brain mitochondrial function.

BACKGROUND Hemangioblastoma typically occurs in the cerebellum, spinal cord, and central nervous system. However, in rare cases, it could occur in the retina or optic nerve. The prevalence of retinal hemangioblastoma is 1 in 73080, and it occurs either alone or as the manifestation of von Hippel Lindau (VHL) disease. Here, we reported a rare case with the imaging features of retinal hemangioblastoma without VHL syndrome, along with the relevant literature review. CASE SUMMARY A 53-year-old man had progressive swelling, pain and blurred vision in the left eye without obvious inducement for 15 d. Ultrasonography revealed a possible optic nerve head melanoma. Computed tomography (CT) showed punctate calcification on the posterior wall of the left eye ring and small patchy soft tissue density in the posterior part of the eyeball. Magnetic resonance imaging showed slightly hyperintense signal on T1-weighted images and slightly hypointense-to-isointense signal on T2-weighted images at the medial and posterior edges of the left eyeball, a significant enhancement was observed in the contrast-enhanced scans. Positron emission tomography/CT fusion images showed that the glucose metabolism of the lesion was normal. Pathology was consistent with hemangioblastoma. CONCLUSION Early identification of retinal hemangioblastoma based on imaging features is of great value for its personalized treatment.

Background: In order to reduce the occurrence of bone cement leakage, bone filling mesh container technique can be a prior choice for the treatment of vertebral metastases with damaged posterior margin of the thoracolumbar vertebral body. Objectives: The purpose of this retrospective study was to compare the efficacy and safety of percutaneous balloon kyphoplasty (PKP) and bone filling mesh containers (BFMCS) in the treatment of vertebral metastases with posterior vertebral body damage. Patients and Methods: This is a retrospective study. From October 2016 to January 2018, 40 cases (72 vertebral bodies) of thoracolumbar osteolytic metastases were treated with vertebroplasty. Among them, 20 cases (37 vertebral bodies) were treated with PKP (PKP group), and 20 cases (35 vertebral bodies) were treated with BFMCS (BFMCS group). The operation time of the two groups was recorded, and visual analog scale (VAS), Oswestry disability index (ODI), intraoperative bone cement leakage and complications were observed before operation and 1 day, 1 month and 6 months after operation. Results: All patients underwent successful operation. The operation time of the PKP group was 42.65 ± 7.84 minutes, and 42.95±8.48 minutes in the BFMCS group (P = 0.91). Both groups differed significantly when the results were compared with those measured before treatment. VAS dropped from 7.50 ± 0.95 points before operation to 1.20 ± 0.41 points at 6 months follow up in PKP group (P < 0.001), in the BFMCS group VAS dropped from 7.50 ± 0.94 points before operation to 1.45 ± 0.51 points at 6 months after operation (P < 0.001). The ODI of the PKP group dropped from 75.80±4.76 before operation to 12.05 ± 1.47, 6 months after operation (P < 0.001), ODI dropped from 75.00 ± 4.34 before operation to 11.60 ± 1.39 at 6 months follow up in the BFMCS group (P < 0.001). In the PKP group, 15 vertebral bodies (40.5%, 15/37) occurred bone cement leakage, but the patients had no clinical symptoms of bone cement leakage. Cement leakage occurred in one case in the BFMCS group. There were no complications such as pulmonary embolism, paraplegia or perioperative death. Conclusion: The application of bone-filling mesh container for treating patients with thoracolumbar osseointegrated metastases could significantly reduce the leakage rate of bone cement, and is similar to traditional PKP in pain relief and activity improvement.