A novel rabies vaccine based on infectious propagating particles derived from hybrid VEEV-Rabies replicon.

BACKGROUND: Live attenuated vaccines (LAVs) can mimic natural infection and have advantages to stimulate a robust and sustained immune response as well as to confer long-term protection. However, safety concerns is one of the major obstacles for LAVs development. In an effort to achieve the optimal balance between immunogenicity and safety, researchers currently have taken different strategies for the development of LAVs. METHODS: We constructed a novel infectious self-propagating hybrid replicon particle (PRP), VEEV-RABV-G, through replacing the entire structural proteins of the Venezuelan equine encephalitis virus (VEEV) with the glycoprotein of rabies virus (RABV-G) as the single structural protein. We evaluated the potential of VEEV-RABV-G as a safe live attenuated vaccine in mice model. FINDINGS: We found that VEEV-RABV-G could self-propagate efficiently in cell culture and induce a robust humoral immunity and provide protection against virulent RABV challenge in immunized mice. Remarkably, VEEV-RABV-G is highly attenuated in both adult and sucking mice, causing much weaker inflammatory and apoptotic effects in the brains of infected adult mice and significantly lower weight loss and morbidity compared with the commonly used RABV-derived LAVs. INTERPRETATION: This study reveals the feasibility of developing novel rabies vaccines based on the self-replicating PRPs. FUNDING: This work was supported by the National Key Research and Development Program of China (2016YFD0500400).

PALB2 mutations in breast cancer patients from a multi-ethnic region in northwest China.

BACKGROUND: Germline mutations in PALB2 gene make a small contribution to heritable breast cancer susceptibility. A recent report has revealed that women with mutations in the PALB2 gene were more than nine times as likely to develop breast cancer compared to those without. The aim of this study is to understand the status of PALB2 mutations among Chinese high-risk breast cancer patients in a multi-ethnic region in China. METHODS: 152 patients with hereditary predisposition to breast cancer from the Xinjing region of China were enrolled in the study, and 100 control samples from healthy women were collected in the same locality. We sequenced the coding sequences and flanking intronic regions of PALB2 gene from DNA samples obtained from all subjects by direct sequencing. RESULTS: A total of 4 deleterious PALB2 mutations were identified in 152 breast cancer patients with a prevalence of about 2.6 % (4/152). The PALB2 mutation prevalence was 3.2 % (3/95) in cases with family history of breast cancer. In addition to the four deleterious mutations, we identified nine missense variants in 12 patients, using the prediction Softwares SIFT and PolyPhen, four of which might be disease associated (in 5 patients). Two of the 4 patients with deleterious mutations and 2 of the 5 patients presenting putative deleterious missense mutations had triple-negative breast cancer. No PALB2 mutation carriers were identified in 100 healthy controls. CONCLUSION: PALB2 mutations account for a small, but not negligible, proportion of patients with hereditary predisposition to breast cancer in the Xinjing region of China.

[Comparison of ultrasound-guided transrectal and transperineal prostate biopsies in clinical application].

OBJECTIVE: To compare the positive rates and complications of ultrasound-guided transrectal and transperineal prostate biopsies. METHODS: We retrospectively analyzed 156 cases of ultrasound-guided transrectal (n = 97) and transperineal (n = 59) prostate biopsy, and compared the positive rate and post-biopsy complications between the two approaches. RESULTS: The positive rates in the transrectal and transperineal groups were 48.4% and 44.1%, respectively, with no significant difference between the two approaches according to different PSA levels (P >0.05). No statistically significant differences were observed between the transrectal and transperineal groups in the post-biopsy incidence rates of such complications as hematuria (54.6% vs 42.4%, P >0.05), lower urinary tract symptoms (17.5% vs 22.0%, P >0.05), dysuria (9.3% vs 6.8%, P >0.05), and acute urinary retention (7.2% vs 6.8%, P >0.05). However, the incidence rates of post-biopsy infection and rectal bleeding were remarkably higher (15.5% vs 3.4%, P<0.05 and 50.5% vs 3.4%, P >0.01) while that of perineal swelling markedly lower in the former than in the latter (3.1% vs 13.6%, P <0.05). CONCLUSION: Transrectal and transperineal biopsies are both effective for the diagnosis of prostate cancer. Since their complications vary, the choice between the two methods depends on the specific condition of the patient.