Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study.

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS: ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

Global Research Trends in Dental Stem Cells: A Bibliometric and Visualized Study.

Dental stem cells (DSCs) are mesenchymal stem cell-like populations with self-renewal and multidifferentiation potential. These cells have been studied in regenerative medicine and tissue engineering. Despite rapid progress in the past two decades, there has been no bibliometric analysis of DSC research. Here, we performed a comparative study using bibliometric methods for DSCs. A total of 5498 articles were included. Our results showed that the United States was the leader in international cooperation and numbers of citations and was the largest contributor. The Journal of Endodontics published the largest number of articles. The author with the greatest contribution was Songtao Shi. The keywords were mainly related to the fields of tissue engineering and regenerative medicine. Relative research interest and the number of publications increased yearly worldwide. The hotspots of DSC research were transiting from basic research to clinical regenerative medicine. Impact statement Dental stem cells (DSCs) are stem cells with self-renewal and multidirectional differentiation potential. Research in this field is attracting increasing attention. This study aimed to understand the current research status of DSCs and to predict promising keywords and trends. We found the global trend of DSCs and their application in the field of regenerative medicine and tissue engineering. Our study makes a significant contribution to the literature because it will help researchers to understand the research trends and directions in this field.

Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents.

A series of dual dithiocarbamates were synthesized and evaluated for their in-vitro anticancer activities on human non-small cell lung cancer cell line H460. Nine compounds exhibited significant antiproliferative activities with IC50 less than 1 µM. Among them, compound 14m showed the highest inhibitory activity against H460 cell and inhibited the growth of nine types of tumor cells with IC50 values less than 1 µM. It also achieved IC50 of 54 nM and 23 nM against HepG2 and MCF-7 cell lines, respectively. Preliminary structure-activity relationship study indicated that: a) when the methyl group (region A) is substituted with benzene rings, ortho substitution on the benzene ring is favored for activity; b) substitution with heterocyclic structures at region A exhibited greater impact on the anti-tumor activity of compounds, in which pyridine ring, thiazole ring, coumarin and benzo[b]thiophene are favored and quinoline ring is the most favored; c) substitution with different amines (region B) also showed marked effect on the activity of compounds and dimethylamine and morpholine are preferred to other tested amines.

IC-4, a new irreversible EGFR inhibitor, exhibits prominent anti-tumor and anti-angiogenesis activities.

Accumulating evidence suggested that the irreversible tyrosine kinase inhibitors (TKIs) have potential to override the acquired resistance to target-based therapies. Herein, we reported IC-4 as a novel irreversible TKI for epidermal growth factor receptor (EGFR). IC-4 potentially suppressed proliferation, induced apoptosis and a G2/M cell cycle arrest in breast cancer cells, correlating with inhibition of EGF-induced EGFR activation, but independent of DNA damage. In addition, IC-4 exhibited anti-angiogenetic activities both in vitro and in vivo. It suppressed cell viability and proliferation induced by various growth factors in human umbilical vein endothelial cells (HUVECs). IC-4 also inhibited HUVECs migration and tube formation. In transgenic zebrafish embryo model, IC-4 was shown to suppress formation of intersegmental vessel and development of subintestinal vessels. Taken together, these results demonstrated that IC-4 is a new irreversible EGFR-TKI, exhibiting potent anti-breast cancer and anti-angiogenetic effects.

[Comparison and analysis between P(ST) and F(ST) of mitten crabs in the Minjiang River].

Recently, differentiation in phenotypic traits (P(ST)) and differentiation at neutral molecular markers (F(ST)) across populations have been become an important topic in evolutionary biology. The Minjiang River is a key genetic introgression zone between the Chinese mitten crab (Eriocheir sinensis) and the Hepu mitten crab (Eriocheir hepuensis), making it an excellent area to study their genetics and evolutionary mechanisms. We compared and analyzed P(ST) in 14 phenotypic traits and F(ST) in six microsatellite markers from 133 individuals of the mitten crab, sampled in the Minjiang River in 2009 and 2010. The results indicated that 11 phenotypic traits were significantly different (P<0.01) between the 2009 and 2010 populations. The mean expected heterozygosity (H(E)) of the 2009 populations was significantly higher (P=0.008) than that of 2010 populations, but the mean allele richness (A(R)), observed heterozygosity (H( O)) and inbreeding coefficient (F(IS)) were all not significant between 2009 and 2010 populations (P=0.136-0.675). F(ST) in microsatellite markers was 0.1429 between the two years. In the 14 traits, only one trait (F2) was found with P(ST)F(ST), suggesting that directional selection is occurring. This study provides valuable data to the further study and analysis of the molecular evolution of the mitten crab, and contributes a useful reference in comparing P(ST) and F(ST) in other aquatic organisms.