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The purpose of this study is to develop a specific and efficient targeted gene therapy candidate approach for laryngeal carcinomas. Several promoters of human squamous cell carcinoma antigen 2(SCCA2), secretory leukocyte protease inhibitor (SLPI) and Survivin genes were cloned from human genomic DNA and evaluated for tumor-specific transcription potential in human laryngeal carcinoma Hep-2 cells by dual luciferase assays. One SLPI promoter fragment (677 bp) showed the highest efficiency and specificity, and was used to control the expression of a recombinant active caspases-3 (revCasp3), which could trigger apoptosis without activation of its upstream cascade elements once expressed in a cell, in an adenoviral vector (Ad-SLPI-revCasp3), and its antitumor efficacy was assessed. In vitro infection with Ad-SLPI-revCasp3 showed revCasp3 could be specifically expressed in Hep-2 cells, resulting in efficient activation of endogenous Caspase-3 and subsequent apoptosis of Hep-2 cells. In Hep-2 nude mice xenograft model, intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor growth without obvious loss of body weight and obvious hepatic toxicity. In summary, our study showed the specific and efficient apoptosis-inducing potential of Ad-SLPI-revCasp3, and this makes it a new candidate approach of targeted gene therapy for laryngeal squamous cell carcinoma, which needs further systematic investigation.

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Study question Is it safe using aspirin (A) and prednisone (P) before pregnancy among women with antithyroid antibodies (ATAbs) undergoing assisted reproductive technology? Summary answer Combination therapy of aspirin and prednisone didn’t improve likelihood of clinical pregnancy, but increased miscarriage rate. What is known already Compared with women with negative-ATAb, women with positive-ATAb had a lower live birth rate and a higher miscarriage rate. Insufficient evidence existed to determine whether aspirin and prednisone therapy improved the success of pregnancy following assisted reproductive technology (ART) in ATAb-positive euthyroid women. Aspirin and prednisone were used frequently in clinical practice, but the use of these medicines before pregnancy during ART process is still controversial, and the risks of these medicines were not well understood. Study design, size, duration A prospective study involving 268 women with unexplained reason for infertility who tested positive for antithyroperoxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) were being treated for infertility at the Second Affiliated Hospital of Zhejiang University School of Medicine, Ningbo Women and Children’s Hospital and People’s Hospital of Jinhua from October 2017 to July 2020. Their TSH level ranged from 0.35–4.0mIU/ml and they all underwent fresh embryo transfer. Participants/materials, setting, methods Overall, a total of 268 ATAb-positive women were divided 2 groups: group A: no treatment; B: A+P. Both medicines were used in the lowest effective dose. Between the two groups, we measured oocytes retrieved, fertilization rate, high-quality embryo rate, blastulation rate, cleavage rate,implantation rate, likelihood of clinical pregnancy and miscarriage rate. Kruskal-Wallis test was used in nonnormally distributed variables, and the χ2 test or Fisher exact test was used to compare categorical variables. Main results and the role of chance A total of 268 infertile women with unexplained reason who tested positive for TPOAb and/or TgAb were recruited in our study. According to assignment, they were divided into two groups. All women in different groups had the similar age, BMI, number of miscarriage and duration of infertility. Levels of FSH, AMH, TSH, FT4, FT3, fibrinogen and d-dimer were similar in all groups. The use of A+P reduced cleavage rate (F = 23.982, P < 0.001) and implantation rate (F = 4.388, P = 0.036). The fertilization rate (P = 0.407), high-quality embryo rate (P = 0.208) and blastulation rate (P = 0.157) were not influenced by the use of medication. In this study, likelihood of clinical pregnancy (P = 0.066) did not change significantly after therapy, and miscarriage rate (P = 0.042) increased after medical treatment. Limitations, reasons for caution Firstly, Aspirin is just one representation of anticoagulation therapy, so additional consideration of low molecular heparin should also be considered. Secondly, further randomized controlled trials of aspirin and prednisone alone are needed. Wider implications of the findings: In this study, use of A+P showed no positive effect, and reduced cleavage rate and implantation rate, while increased miscarriage rate. So, the use of medication for interfile women should be cautious. Trial registration number n/a