Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective:To analyze the subsequent assisted pregnancy outcomes of recurrent implantation failure (RIF) and find out the key influencing factors.Methods:A case-control study was conducted to analyze the clinical data of 640 patients who received embryo transfer assisted fertility in the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2019 and were diagnosed with RIF and received subsequent assisted fertility treatment. The main outcome measures were the live birth rate and the time to pregnancy after diagnosis of RIF.Results:The live birth rate, the biochemical pregnancy rate, the clinical pregnancy rate and the abortion rate of the first cycle, the second cycle, the third and above cycle after a diagnosis of RIF were not significantly different (all P>0.05). The time to pregnancy after diagnosis of RIF of 344 patients who achieved live births was 5.00(3.13, 8.52) months. After adjusting for confounding factors by using multivariate logistic regression, the results showed that the cumulative live birth probability of blastocyst transfer was significantly higher than that of cleavage embryo transfer [ P=0.002, RR (95% CI)=1.492(1.158-1.923)]; the cumulative live birth probability of patients less than 35 years old was significantly higher than older patients (≥35 years old)[ P=0.013, RR (95% CI)=0.694(0.521-0.925)]; the cumulative live birth probability of patients with endometrial thickness ≥8 mm on the embyro transfer day was significantly higher than that of patients with endometrial thickness <8 mm [ P=0.016, RR (95% CI)=1.943(1.132-3.335)]; compared with patients with 0 [ P=0.001, RR (95% CI)=0.625(0.474-0.825)] or 2 and more [ P=0.003, RR (95% CI)=0.414(0.233-0.736)] biochemical pregnancy in the RIF cycles, the cumulative live birth probability of patients with history of only 1 biochemical pregnancy in the RIF cycles was significantly higher. Conclusion:The type of embryos transferred, age, endometrial thickness on the embyro transfer day and the history of biochemical pregnancy in the RIF cycles are independent factors for subsequent cumulative live birth probability in RIF patients. Blastocyst transfer should be selected as much as possible, and fertility treatment should be performed as soon as possible through reasonable cycle management, the history of only 1 biochemical pregnancy in the RIF cycles heralds a better live birth outcome in the subsequent cycles of RIF.

Objective:To analyze the subsequent assisted pregnancy outcomes of recurrent implantation failure (RIF) and find out the key influencing factors.Methods:A case-control study was conducted to analyze the clinical data of 640 patients who received embryo transfer assisted fertility in the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2019 and were diagnosed with RIF and received subsequent assisted fertility treatment. The main outcome measures were the live birth rate and the time to pregnancy after diagnosis of RIF.Results:The live birth rate, the biochemical pregnancy rate, the clinical pregnancy rate and the abortion rate of the first cycle, the second cycle, the third and above cycle after a diagnosis of RIF were not significantly different (all P>0.05). The time to pregnancy after diagnosis of RIF of 344 patients who achieved live births was 5.00(3.13, 8.52) months. After adjusting for confounding factors by using multivariate logistic regression, the results showed that the cumulative live birth probability of blastocyst transfer was significantly higher than that of cleavage embryo transfer [ P=0.002, RR (95% CI)=1.492(1.158-1.923)]; the cumulative live birth probability of patients less than 35 years old was significantly higher than older patients (≥35 years old)[ P=0.013, RR (95% CI)=0.694(0.521-0.925)]; the cumulative live birth probability of patients with endometrial thickness ≥8 mm on the embyro transfer day was significantly higher than that of patients with endometrial thickness <8 mm [ P=0.016, RR (95% CI)=1.943(1.132-3.335)]; compared with patients with 0 [ P=0.001, RR (95% CI)=0.625(0.474-0.825)] or 2 and more [ P=0.003, RR (95% CI)=0.414(0.233-0.736)] biochemical pregnancy in the RIF cycles, the cumulative live birth probability of patients with history of only 1 biochemical pregnancy in the RIF cycles was significantly higher. Conclusion:The type of embryos transferred, age, endometrial thickness on the embyro transfer day and the history of biochemical pregnancy in the RIF cycles are independent factors for subsequent cumulative live birth probability in RIF patients. Blastocyst transfer should be selected as much as possible, and fertility treatment should be performed as soon as possible through reasonable cycle management, the history of only 1 biochemical pregnancy in the RIF cycles heralds a better live birth outcome in the subsequent cycles of RIF.

OBJECTIVETo explore the influences of di-(2-ethylhexyl)phthalate (DEHP) and its principle metabolite mono(2-ethylhexyl)phthalate (MEHP) on spermatogenic cell apoptosis in young male Wistar rats.

METHODSNinety-eight 2-week-old male Wistar rats were randomly divided into 14 equal groups to receive daily intragastric administration of 0.2 ml/kg normal saline for 3 weeks (normal control), 100 mg/kg cyclophosphamide (CTX) for 1 week (positive control), 100, 200, and 300 mg/kg DEHP or MEHP for 1 week, or 100 mg/kg DEHP or MEHP for 1, 2, and 3 weeks. After the treatments, the pathological changes of the testicular tissues were examined, spermatogenic cell apoptosis was detected, and serum sex hormones levels were measured using TUNEL assay or radioimmunoassays.

RESULTSCTX, DEHP, and MEHP all caused shrinkage, development retardation and quantitative reduction of spermatogenic cells with and mitochondrial swelling vacuolar changes. The damage of spermatogenic cells increased significantly with the increment of DEHP and MEHP doses and exposure time. Both DEHP and MEHP treatments resulted in significantly increased cell apoptosis index (AI) in close correlation with the exposure doses and duration (P<0.01). DEHP and MEHP treatments also significantly increased serum levels of follicle stimulating hormone and luteinizing hormone and decreased testosterone levels in a dose- and time-dependent manner (P<0.05).

CONCLUSIONDEHP and MEHP can induce obvious apoptosis of spermatogenic cells in young male rats with a dose- and time-dependent effect.

Animals ; Apoptosis ; drug effects ; Diethylhexyl Phthalate ; analogs & derivatives ; toxicity ; Dose-Response Relationship, Drug ; Environmental Exposure ; Male ; Rats ; Rats, Wistar ; Spermatozoa ; cytology ; drug effects

Objective To understand the clinical significance and diagnosis value of serum interleukin-6(IL-6) levels in the patients with respiratory infection and non-small cell lung cancer(NSCLC).Methods The serum levels of IL-6 in 61 patients with NSCLC,and 36 patients with respiratory infection and 30 of the healthy was measured by enzyme-linked immunosorbent assay(ELISA).Results The data showed that mean serum IL-6 levels in patients with NSCLC was higher than in the healthy( P 0 05).Conclusion We consider that increased IL-6 level could be used as one of differential diagnostic marker of NSCLC;Serum IL-6 levels may be a reference of judging each stage of NSCLC and predicting prognosis.