Comparison between oral dydrogesterone versus micronized vaginal progesterone gel in clinical outcome within the first HRT-FET cycle: a retrospective analysis.

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

Controlling Electron/Hole Recombination in Near-Infrared Polymer Phototransistors through an Insulation Medium: A Pathway to Ultrahigh Photosensitivity.

In near-infrared (NIR) polymer phototransistors, the photoresponse is proportional to the turn-on voltage shift (ΔVth). Due to the narrow band gap of NIR polymers, the ΔVth value is usually small. However, the use of a single bulk heterojunction (BHJ) layer has a minimal effect on increasing the value of ΔVth. This is because doping with high concentrations of acceptors results in strong current traps and accelerates electron/hole recombination. In this work, a new strategy is proposed to control the recombination of electrons/holes. By doping an insulating medium made of polystyrene (PS) into BHJs, PC61BM:PS:PDPP3T-based ternary NIR phototransistors with high acceptor concentrations were prepared by using a one-step film transfer method (FTM). Compared with a PC61BM:PDPP3T-based binary device (1:1), a ternary device (1:1:1) exhibited a significant performance improvement. The ΔVth value (∼29.5 ± 1.0 V) increased by approximately 4-fold, the Iph/Idark (∼4.4 × 106) increased by a factor of 3000 to 4000-fold, and the dark current decreased by 2-3 orders of magnitude (@ Vg = 0 V). Additionally, the ternary devices demonstrated excellent performance across a wide ternary ratio range (1:1:1 to 4:2:1).

Impact of Pre-Stroke Dementia or Mild Cognitive Impairment on Stroke Outcome: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Pre-stroke dementia (PSD) and pre-stroke mild cognitive impairment (PSMCI) are important risk factors for stroke. The present meta-analysis aimed to investigate the impact of PSD or PSMCI on stroke outcomes. METHODS: Electronic databases (PubMed, EMbase, Google Scholar, Cochrane Library, and TRIP) were screened for eligible studies published prior to March 31, 2021. Risk ratios (RR) and mean differences with 95% confidence intervals (CIs) using random or fixed effect models were used to calculate pooled estimates. Study quality was assessed using the Newcastle Ottawa Scale. RESULTS: Fifteen studies were included in our meta-analysis. Pooled data from ten studies involving 3,107 PSD and 20,645 non-PSD subjects showed a higher risk of mortality in PSD patients (RR = 2.03; 95% CI: 1.40-2.91; I2 = 89%). Risk of recurrent stroke risk was observed more in patients with PSD compared to non-PSD patients (RR = 2.02; 95% CI: 1.40-2.91; I2 = 0%). Three studies involving 300 mild cognitive impairment (MCI) and 1,025 normal cognition subjects showed a significant increased risk of mortality in stroke patients with MCI (RR = 2.43; 95% CI: 1.81-3.27; I2 = 20%). However, elevated stroke severity was not observed in PSMCI patients. CONCLUSIONS: Our meta-analysis shows an increased risk of mortality in stroke patients with a history of PSD and PSMCI. Proper clinical management and increased attention are therefore required for the prevention and management of stroke in patients with cognitive deficits.

Diffusion interface layer controlling the acceptor phase of bilayer near-infrared polymer phototransistors with ultrahigh photosensitivity.

The narrow bandgap of near-infrared (NIR) polymers is a major barrier to improving the performance of NIR phototransistors. The existing technique for overcoming this barrier is to construct a bilayer device (channel layer/bulk heterojunction (BHJ) layer). However, acceptor phases of the BHJ dissolve into the channel layer and are randomly distributed by the spin-coating method, resulting in turn-on voltages (Vo) and off-state dark currents remaining at a high level. In this work, a diffusion interface layer is formed between the channel layer and BHJ layer after treating the film transfer method (FTM)-based NIR phototransistors with solvent vapor annealing (SVA). The newly formed diffusion interface layer makes it possible to control the acceptor phase distribution. The performance of the FTM-based device improves after SVA. Vo decreases from 26 V to zero, and the dark currents decrease by one order of magnitude. The photosensitivity (Iph/Idark) increases from 22 to 1.7 × 107.

Differentiation of primordial germ cells from premature ovarian insufficiency-derived induced pluripotent stem cells.

BACKGROUND: Premature ovarian insufficiency (POI) is a common disease in reproductive women. The pathogenesis of POI is not clear, although it is known that it involves the disorder of oocyte differentiation and development. The introduction of reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) offers a unique opportunity to study many aspects of POI from cell differentiation in vitro that could ultimately lead to novel drug development and testing to help treat the disorder. METHODS: The fibroblasts from POI patients, including fragile X syndrome, abnormal karyotype (45, X; 45, X/46, XX; 45, XO and 47, XXX), and the gene mutation (FIGLA and GDF9) were reprogrammed to pluripotency status by retroviral transduction using defined factors. The morphology, growth characteristics, gene expression profiles, epigenetic status, and in vitro and in vivo differentiation potential of the POI-1-iPSCs (from fragile X syndrome) were analyzed. Then, POI-1-iPSCs were induced to differentiation into primordial germ cells (PGCs) with DNA methyltransferase inhibitors. RESULTS: The iPSCs were successfully generated from POI patients' fibroblasts. The formed iPS clones have the same characteristics of human ESCs. POI-1-iPSCs were successfully generated with germline competence. The POI-1-iPSCs, with genotypes of fragile X syndrome, can be induced to differentiation into PGCs with high efficiency under our culture system by DNA demethylation. This study proved that disease-specific iPSC lines derived from POI patients could be generated and successfully differentiated into PGCs. CONCLUSIONS: We established some novel, systemic cell models for the studying of the pathogenesis of POI patients. Second, DNA demethylation may accelerate the induction of human PGCs from iPSCs in vitro and the conclusion needs further exploration. This represents an important step in the novel approach for the study of the pathophysiology and potential egg resource for POI patients.

Genetic Manipulation by Zinc-Finger Nucleases in Rat-Induced Pluripotent Stem Cells.

Induced pluripotent stem cells (iPSCs) have an extensive application in regenerative medicine, pharmaceutical discovery, and basic research. With the recent derivation of rat iPSCs, it is now feasible to apply genetic manipulation in this species. But such tools do not yet exist for many rat strains, especially for disease model rat. The Sprague Dawley (SD) rat is an inbred disease model for hypertension, nephropathy, pulmonary hypertension, depression, and alcohol consumption. In this study, the SD rat iPSCs were generated using lentiviral method. The p53 gene was targeted in rat iPSCs using homologous recombination mediated by P53 zinc-finger nucleases (ZFNs). Our results showed that these rat iPSCs were pluripotent status. P53 gene was targeted successfully with high efficiency by coelectroporating the donor targeting vectors and p53 ZFN vector to these rat iPSCs. Southern blotting analysis confirmed the correct homologous recombination in rat iPSCs. At the same time, our results demonstrated that the P53 dependent function was abolished in p53-targeted iPSCs. This report also demonstrated that iPS technology, combined with homologous recombination mediated by ZFN, was suitable to develop human disease model in rat and other species.

Establishment and adipocyte differentiation of polycystic ovary syndrome-derived induced pluripotent stem cells.

OBJECTIVE: To establish a new biological cell model and approach to mimic abnormal lipid metabolism of polycystic ovary syndrome (PCOS) in vitro. MATERIALS AND METHODS: Epithelial cells from PCOS patients were reprogrammed to pluripotency by retroviral transduction using defined factors. Morphology, growth characteristics, karyotype, gene expression and differentiation in vitro and in vivo were detected by identification protocol of human embryonic stem cells (ESCs). PCOS-induced pluripotent stem cells (iPSCs) were then induced to differentiate into adipocytes. Ability of the adipocytes for glucose consumption was compared with those from non-PCOS-iPSCs. RESULTS: iPSCs were successfully generated from PCOS patients' adult cells. Formed iPSC clones had the same characteristics of human ESCs. PCOS-iPSCs were induced to differentiation into normal karyotype adipocytes. Compared to non-PCOS-iPSCs, PCOS-iPSCs had more glucose consumption ability during adipocyte differentiation and development in vitro. CONCLUSIONS: This protocol provides a new biological cell model and approach for studying pathogenesis of PCOS and discovering potential drugs to treat it.

Discovery of piperidine-linked pyridine analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

In our continued efforts to discover more active and less toxic HIV-1 non-nucleoside reverse transcriptase inhibitors, we recently designed a novel series of piperidine-linked pyridine analogues on the basis of diarylpyrimidine derivatives, among which two drugs-etravirine and rilpivirine-are approved for use by the US FDA. The title compounds were evaluated for activity against wild-type and resistant mutant strains of HIV-1 as well as HIV-2 in MT-4 cells. The highly potent compound BD-c1 (EC50 =10 nM, CC50 ≥146 µM, SI≥14 126) displays lower cytotoxicity and higher selectivity than etravirine (EC50 =2.2 nM, CC50 =28 µM, SI=12 884) against wild-type HIV-1. Compound BD-e2 (EC50 =5.1 nM) shows greater antiviral efficacy against wild-type HIV-1 than do the four reference drugs nevirapine, delavirdine, efavirenz, and zidovudine. Many compounds were also found to be active against the frequently observed drug-resistant double mutant (K103N+Y181C) HIV-1 strain. Herein we report the design, synthesis, anti-HIV evaluation, preliminary structure-activity relationships, and molecular simulations of novel piperidine-linked pyridine analogues.

Recent advances of diaryl ether family as HIV-1 non-nucleoside reverse transcriptase inhibitors.

Diaryl ether family as one of the promising second generation HIV-1 non-nucleoside reverse transcriptase inhibitors has attracted considerable attention over the past few years, among which clinical candidate MK-4965 has been advanced into phase II clinical trials. The successful development of diaryl ether family provides valuable avenues in traditional medicinal chemistry, crystallography and computer-aided drug design fields for the design of other novel anti-HIV drug candidates. In this review, the development of diaryl ether family is present including the evolutionary history, design strategies, extensive structural modifications, structure-activity relationship studies and computer-aided molecular simulation of the binding mode in detail.

Use of amniocytes for prenatal diagnosis of 22q11.2 microdeletion syndrome: a feasibility study.

BACKGROUND: A study of prenatal genetic diagnosis for 22q11.2 microdeletion, which has a wide phenotypic spectrum that involves almost all organs, is rarely reported in China. This study aimed to explore the prevalence of 22q11.2 microdeletion in congenitally malformed fetuses via the fluorescent in situ hybridization (FISH) technique and to investigate the feasibility of use of amniocytes to diagnose 22q11.2 microdeletion syndrome prenatally. METHODS: The study enrolled 23 cases of fetal cardiac malformation, as indicated by ultrasound in Beijing Anzhen Hospital and 14 cases of non-cardiac malformation, as determined by type-B ultrasound in Beijing Anzhen Hospital and other hospitals. Amniotic fluid was obtained by amniocentesis before odinopoeia, and the stillborn fetuses of the induced labor were preceded to autopsy. The amniotic fluid of 20 cesarean deliveries during the same period of time was used as a control. The TUPLE1 gene in the amniotic fluid of malformed and normal fetuses was assessed by the FISH method. RESULTS: The prevalence rates of the TUPLE1 gene deletion in the amniotic fluid cells from fetuses with cardiac deformations and fetuses without such malformations were 43.5% and 57.1%, respectively. The deletion of TUPLE1 was significantly associated with fetal malformation. CONCLUSION: Chromosome 22q11.2 microdeletion is one of the major factors leading to fetal congenital malformations, and prenatal FISH screening for 22q11.2 microdeletion syndrome is technically feasible using amniocytes.