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This study is intended to investigate oral exostoses of 5 sample populations, spanning over 6000 years, from the same region of Northern China, to determine the significance of sex and age on the development of oral exostoses during each time period. The samples analyzed were 306 dry jaws from human skeletons, which were excavated from 4 archeological sites: Banpo (6700–5600 y BP), Shaolingyuan (3000 y BP), Shanren (2200 y BP), and Chang’an (1000–1300 y BP), as well as the modern Xi’an district. The sex and the age of the samples at death were estimated. The degree of buccal exostosis (BE), torus mandibularis (TM), and torus palatinus (TP) and the TP shape were recorded. The results showed BEs in the Banpo and Chang’an regions, TMs in the Banpo region were more often diagnosed in males than in females. Conversely, females in Shaolingyuan showed a higher prevalence and severity of TM than that in males. The occurrence of BEs in the Shanren and Xi’an regions, TMs in the Banpo, Chang’an, and Xi’an regions, as well as TPs in the Banpo region significantly increased with age at death. In conclusion, sex differences and increasing trends with age in relation to oral exostoses were found in samples from Northern China during the past six millennia.

The role of programmed cell death-ligand 1 (PD-L1) in cervical cancer has been widely investigated; however, the influences of other inhibitory B7 family members are poorly understood. We investigated the expression of PD-L1, B7 homolog 3 (B7-H3), B7-H4, and V-domain Ig suppressor of T-cell activation (VISTA) and their association with the clinicopathological features and outcomes of a large cohort of 673 patients with squamous cell carcinoma or adenocarcinoma of the uterine cervix. The positivity rates for PD-L1 (combined positive score ≥1), B7-H3 in tumor cells (TCs), B7-H4 (exclusively in TCs), VISTA in immune cells (ICs), and VISTA in TCs were 57.9%, 62.8%, 44.8%, 92.6%, and 4.8%, respectively, in 606 primary cervical cancer samples. Co-expression of PD-L1 with B7-H3 in TCs and with B7-H4 and VISTA in ICs was observed in 38.8%, 25.4%, and 57.9% of samples, respectively. B7-H3 in TCs and B7-H4 and VISTA in ICs were observed in 58.1%, 46.6%, and 83.1% of PD-L1-negative samples, respectively. These proteins were observed more frequently in squamous cell carcinomas and in moderately to poorly differentiated carcinomas. VISTA (in ICs) and B7-H4 were more frequent in primary tumors than in recurrent counterparts and correlated with improved survival; in contrast, B7-H3 positivity in TCs was less frequent in primary tumors and correlated with short disease-specific survival. Co-expression of B7-H4 and VISTA in ICs was an independent predictor of favorable outcomes overall and among patients with PD-L1-negative tumors. These data indicate that B7 family proteins exhibit differing expression patterns, distributions, and prognostic implications in cervical cancer. Furthermore, the co-expression of PD-L1 with other checkpoint proteins suggests that PD-1/PD-L1 blockade combined with modulating other immune checkpoints may present a novel therapeutic approach for cervical cancer. Future studies are needed to validate prognostic values of B7 family proteins and explore their biological roles in this malignancy.

abstractHuman enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P< 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6–36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile.

Streptococcus pneumoniaeis an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. Vaccines have become the most effective way to prevent pneumococcal infections. This phase III trial was designed to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years. We conducted a randomized, double-blinded, active-controlled, multicenter trial in which 1660 healthy population (>2 years of age) were randomly assigned in a 1 : 1 ratio to receive 2 intramuscular doses of either the treatment vaccine or the active control vaccine, PNEUMOVAX 23. The surveillance period was 30 days. The primary end point was the 2-fold increase rate of anti-pneumococcal antibody for all 23 included serotypes in each group. In the intention-to-treat cohort, the 2-fold increase rate of anti-pneumococcal antibody for 23 included serotypes varied from 62.47% to 97.01% in the treatment group, and from 51.49% to 95.77% in the control group. According to −10% non-inferiority margin and 95% confidence intervals of rate difference, almost all included serotypes of the treatment group reached non-inferiority to control group except for serotype 6B, the lower limit of rate difference of which was −10.00%, equal to the non-inferiority margin. The 2-fold increase rates of anti-pneumococcal antibody were significantly higher in the treatment group for serotype 2, 3, 4, 10A, 11A and 20. Furthermore, for all 23 serotypes, IgG geometric mean concentrations (GMCs) at day 30 were significantly higher in treatment group for serotype 2, 3, 4, 9V, 10A, 11A, 15B, 18C, 19A, 22F and 33F. Higher geometric mean fold increase (GMFI) were also observed in the treatment group correspondingly. Serious adverse events occurred in 3 of 830 participants in the treatment group (0.36%) and 2 of 830 participants in the control group (0.24%). No death occurred during the trial. The frequencies of both solicited and unsolicited adverse events (AEs) were small lower in the treatment group (34.34% vs35.66% for solicited AEs, 4.34% vs5.42% for unsolicited AEs). Both vaccines were well tolerated and most AEs were mild or moderate in intensity. The newly vaccine was well tolerated and immunologically non-inferior to the active control vaccine PNEUMOVAX 23 for all 23 vaccine serotypes in the Chinese population (>2 years of age).