[Application of seamless phase â ¡/â ¢ design in vaccine clinical trials].

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

[The comparison of modified ESUR score and Mehralivand grade based on biparametric MRI for assessing extracapsulare extension in prostate cancer].

Objective: To compare the value of the modified European Society of Urogenital Radiology (ESUR) score and Mehralivand grade based on biparametric MRI (bpMRI) in the assessment of extracapsular extension (ECE) in patients with prostate cancer (PCa). Methods: Data of 235 patients with postoperative pathology confirmed PCa, who underwent preoperative 3.0 T bpMRI examinations between March 2019 and March 2022 in the First Affiliated Hospital of Soochow University were retrospectively evaluated, including 107 ECE positive and 128 ECE negative cases, aged [M (Q1, Q3)] [71 (66, 75)] years. Reader 1 and 2 assessed the ECE using the modified ESUR score and Mehralivand grade, and the receiver operating characteristic curve and Delong test were used to evaluate the performance of the two scoring methods. Then, the statistically significant variables were included in multivariate binary logistics regression analysis to obtain the risk factors, which were combined with the scores of reader 1 to establish combined models. The assessment ability of the two combined models and the two scoring methods were compared subsequently. Results: The AUC of Mehralivand grade in reader 1 were higher than that of the modified ESUR score in reader 1 and 2 [0.746 (95%CI: 0.685-0.800) vs 0.696 (95%CI: 0.633-0.754) and 0.691 (95%CI: 0.627-0.749), both P<0.05]. The AUC of Mehralivand grade in reader 2 was higher than that of the modified ESUR score in reader 1 and 2 [0.753 (95%CI: 0.693-0.807) vs 0.696 (95%CI: 0.633-0.754) and 0.691 (95%CI: 0.627-0.749), both P<0.05]. The AUC of the combined model 1 based on the modified ESUR score and the combined model 2 based on Mehralivand grade were higher than that in the separate modified ESUR score [0.826 (95%CI: 0.773-0.879) and 0.841 (95%CI: 0.790-0.892) vs 0.696 (95%CI: 0.633-0.754), both P<0.001], and also higher than that in the separate Mehralivand grade [0.826 (95%CI: 0.773-0.879) and 0.841 (95%CI: 0.790-0.892) vs 0.746 (95%CI: 0.685-0.800), both P<0.05]. Conclusion: Based on bpMRI, the Mehralivand grade showed better diagnostic performance for assessing ECE preoperatively in patients with PCa than the modified ESUR score. The combination model of scoring methods and clinical variables can further enhance the diagnostic certainty in the assessment of ECE.

[Application of cluster randomization design in vaccine clinical trials].

When the coverage of the vaccinated people reaches a certain percentage of the population, the herd protection will protect the unvaccinated persons. However, the traditional clinical evaluation of vaccines performing individual randomized design fails to evaluate the herd protection of vaccines. Compared with the individual randomized design, the cluster-randomized design can determine the overall protection by the vaccine more comprehensively. It has become increasingly common to perform a cluster-randomized design in clinical trials of vaccines in Phase Ⅲ and Ⅳ clinical trials. However, little is known about the application of cluster randomized design in vaccine clinical trials in China. We, at this moment, do a review of the application of random cluster design in vaccine clinical trials and provide references for future research in China.

[Application of test-negative design in vaccine efficacy evaluation].

Vaccine efficacy can be assessed by a randomized placebo-control trial prior to marketing. However, after the marketing of a vaccine, if a placebo-randomized control trial is used to evaluate the efficacy of the vaccine, ethical issues will arise. Therefore, the evaluation of the efficacy of a vaccine after marketing has become a difficult problem in the public health field. In recent years, the research method of test-negative design has been widely used in the world for the evaluations of the efficacies of different post-marketing vaccines, such as influenza vaccine, rotavirus vaccine, cholera vaccine, pneumonia vaccine and EV71 vaccine. However, there are limited reports in the domestic literature on the test-negative design. Therefore, we summarize the basic principles, application steps, advantages and disadvantages of the test-negative design to provide theoretical methods and basis for the future study of test-negative design in China.

[Meta-analysis on effectiveness of live attenuated influenza vaccine against seasonal influenza in children].

Objective: To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years. Methods: Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis. Results: A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49% (95%CI: 40%-57%). Subgroup analysis found that the protection rate of LAIV was 35% against influenza A (H1N1) pdm09 (95%CI: 5%-56%), 35% against influenza A (H3N2) (95%CI: 21%-46%), and 71% against influenza B (95%CI: 55%-82%). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56% (95%CI: 48%-63%) and 44% (95%CI: 27%-57%), respectively. The protection rates of LAIV in Europe and North America were 65% (95%CI: 47%-77%) and 46% (95%CI: 36%-55%), respectively. Conclusion: LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.

Antifungal activity of the bioactive substance from Bacillus atrophaeus strain HAB-5 and its toxicity assessment on Danio rerio.

The prevalence of pathogen inhibitors bacteria has motivate the study for antimicrobial compounds. Bioactive fungicide have always received considerable attention. A bacterial isolated strain HAB-5 showed antifungal activity against plant fungi. Based on morphological, physiological, biochemical and 16SrDNA sequence analysis, the strain was identified to be a Bacillus atrophaeus. This strain possessed a broad spectrum antifungal activity against various plant pathogenic fungi. Extraction of antifungal substance was performed and the crude extract had potent antifungal ability and showed great potential for swelling and inhibiting spore germination. This antifungal displayed heat stability and active in a wide pH range 5.0-10.0. Moreover no reduction was found in its activity after enzyme treatment. The toxicity test was evaluated in Danio rerio. The acute toxicity test indicated that the 24, 48, 72, 96h LC50 values of UMTLS to the zebrafish were 14.4, 13.8, 13.4, and 12.9%, respectively. Based on the results obtained in this study, antifungal substance was not toxic to zebra. Analyses of disease suppression showed that HAB-5 was effective to reduce the incidence of anthracnose symptoms on mango fruits, also prevent disease infection and protect tobacco seedling from Phytophtora nicotianae. The bioactive substance from Bacillus atrophaeus HAB-5 could be a candidate in the generation of new antifungal agents in crop.

[Progress in assessment of vaccine on herd protection].

The importance of vaccine on public health is related to the herd protection related to the levels of vaccine coverage, which directly influences the vaccinated individuals as well as the unvaccinated community. Reaching the level of herd protection by increasing vaccine coverage is the basic strategy to eradicate related infectious diseases. Again, herd protection has played an important role in public health practices. With the increasing interests in estimating the vaccine herd protection, we however, have seen only few relevant papers including observational population-based and cluster-randomized clinical trials reported in China. We hope to discuss the study designs for evaluating the vaccine herd protection in order to generate evidence-based related research in this field.

Methylation differences and expression profiles of the caprine DIO3 gene.

DIO3 gene encoding type 3 iodothyronine deiodinase is an imprinted gene, located in the DLK1-DIO3 (delta-like 1 homolog-type 3 iodothyronine deiodinase) imprinted domain, and is potentially involved in degrading excessive amounts of thyroid hormone to protect embryogenesis. However, the underlying regulatory mechanism of the imprinted DIO3 gene expression during fetal and neonatal development in goats has not been elucidated. In this study, we explored the DNA methylation patterns of the caprine DIO3 intragenic CpG island and quantified gene expression level in six tissues from Chinese Nanjiang Yellow 3-day old kids. The expression of the DIO3 gene was determined using quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), while the identification of methylation patterns was determined using bisulfite-sequencing PCRs. Modest, and non-significant (P > 0.05), methylation patterns were noted for the DIO3 CpG island methylation in the brain, heart, liver, kidney, lung, and longissimus dorsi tissues (ranging from 26.48 to 34.92%). The expression level of the DIO3 mRNA was significantly higher (P < 0.05) in the liver tissue than in the other five tissues. Pearson's correlation analysis revealed that there was no significant relationship between methylation and gene expression (P > 0.05), which indicated that the expression of the caprine DIO3 gene was likely modified by other regulatory elements. This study identified DNA methylation and expression patterns of the DIO3 gene in goats and provided insights into further regulatory mechanisms of expression and imprinting in the DLK1-DIO3 domain.