PGT has been widely applied in the world, but its effectiveness for the treatments of recurrent pregnancy loss is still inconclusive. There is currently no consensus over the precise definition of ...RPL, according to the ESHRE guideline in 2022, a diagnosis of Recurrent Pregnancy Loss (RPL) could be considered after the loss of two or more pregnancies. The etiology of RPL is complex and highly heterogeneous, the higher proportion of embryo aneuploidy is an important reason, which can be affected significantly by maternal age. RPL has been listed as one of the common indications for PGT-A worldwide. However, the new RPL guideline by EHSRE in 2022, indicated that limited evidence for PGT in couples with RPL shows no clear benefit of treatment with very low quality. We reviewed the published studies, three retrospective studies showed that PGT-A may improve live birth rate for RPL patients, while two studies showed negative results. Most importantly, there were no randomized studies published on the application of PGT-A among RPL couples. Our data also showed similar cumulative live birth rates between PGT-A group and the control, regardless of maternal age, but PGT-A may favour in reducing miscarriage recurrence risk for RPL couples over 37 years old who obtained transferrable embryos. The presence of mosaic embryos and false positive/negative results, which can cause a high rate of cycle cancellation, may be the main reasons that compromise the efficacy of PGT-A. The cost-effectiveness of PGT-A is another important concern. In conclusion, there is still no sufficient evidence to support whether PGT-A can effectively improve the pregnancy outcomes for RPL couples, and proper-designed RCT is required in the future.
The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the ...live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.
In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.
Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval CI, 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).
Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).
Abstract
As the important equipment of mine production, the level of mine vehicles management has a direct impact on all aspects of production, safety and management of mine. The application of ...IoV(internet of vehicles) to improve the intelligent level of mine vehicle management is an important part of intelligent mine construction. In order to avoid the problems of scattered development, repeated construction and difficult system integration caused by unclear concept, different objectives, different paths, different system architecture and different technical application emphases in the application of IoV in the mine vehicle management, taking the intelligent coal mine as an example, the concept of MIoV (mine internet of vehicles) is proposed, and its system architecture, key technologies and typical applications are analyzed and discussed. Firstly, on the basis of reviewing the development of intelligent mine and IoV, the concept of MIoV is defined and expounded; secondly, referring to the architecture of IoV and MIoT (mine internet of things), the architecture of MIoV is designed, which is composed of sense and control layer, network layer, service support layer and application layer; the key technologies of MIoV and intelligent mine information system are integrated and analyzed key technologies such as positioning and monitoring, intelligent perception and control, wireless communication, collaborative computing. Finally, from the four aspects of human-vehicle-environment-management, mine vehicle and driver monitoring, mine vehicle automatic driving and driverless, mine safety monitoring based on mine vehicles, mine vehicle intelligent scheduling and other typical application of MIoV are discussed. The research results laid a foundation for the construction of MIoV to promote the in-depth and orderly application of IoV in intelligent mine vehicle management, enrich the technical connotation of MIoT, and accumulate experience for the application of other technology branches of MIoT in intelligent mine construction.
Subarachnoid hemorrhage (SAH), predominantly caused by a ruptured aneurysm, is a devastating neurological disease that has a morbidity and mortality rate higher than 50 %. Most of the traditional in ...vivo research has focused on the pathophysiological or morphological changes of large arteries after intracisternal blood injection. This was due to a widely held assumption that delayed vasospasm following SAH was the major cause of delayed cerebral ischemia and poor outcome. However, the results of the CONSCIOUS-1 trial implicated some other pathophysiological factors, independent of angiographic vasospasm, in contributing to the poor clinical outcome. The term early brain injury (EBI) has been coined and describes the immediate injury to the brain after SAH, before onset of delayed vasospasm. During the EBI period, a ruptured aneurysm brings on many physiological derangements such as increasing intracranial pressure, decreased cerebral blood flow, and global cerebral ischemia. These events initiate secondary injuries such as blood–brain barrier disruption, inflammation, and oxidative cascades that all ultimately lead to cell death. Given the fact that the reversal of vasospasm does not appear to improve patient outcome, it could be argued that the treatment of EBI may successfully attenuate some of the devastating secondary injuries and improve the outcome of patients with SAH. In this review, we provide an overview of the major advances in EBI after SAH research.
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•Electrospun quad-axial nanofibers can be fabricated by quadriaxial electrospinning.•The quad-axial configuration of the nanofibers can improve the functionality.•Drugs can be ...encapsulated in the different layers of quad-axial nanofibers.
It is of great importance and a major challenge to achieve a controlled delivery of specific types of active ingredients for tissue regeneration. Herein, we report a system comprised of electrospun quad-axial nanofibers fabricated by quadriaxial electrospinning, with the material components in the different layers can be well regulated. The quad-axial nanofibers allow the regulation of the type of materials in different layers as well as the manipulation of the location of drug in the nanofibers, representing a promising controlled drug release system. In one typical example, we apply polycaprolactone to construct both the outermost and second innermost layers while gelatin to construct both the second outermost and innermost layers. The nanofibers with a cleared four-layered nanostructure are confirmed by morphological evaluations. Moxifloxacin, a type of antibacterial drug serving as a model of therapeutic payload, is encapsulated in the different layers of the nanofibers, realizing an effective control of the drug delivery. In addition, the efficacy for drug delivery with the use of quad-axial nanofibers is superior to that of core-sheath and blended nanofibers. This quadriaxial electrospinning technique can be widely used for the co-delivery of factor cocktails in a designed sequence, which will show great potential for tissue engineering.
MOTION: For Next generation sequencing (NGS) technology has been widely used in the field of genetic diseases, mainly focusing on the diagnosis of genetic diseases, newborn screening, prenatal ...screening, preimplantation genetic test (PGT) and other fields such as the treatment of cancer. In the field of reproductive medicine, there are still some issues that engendered controversy about the application of PGT. On one hand, disputes over whether using PGT to treat late-onset diseases is ethical remain. On the other hand, some tested embryos are “available” to transfer, while others are “discarded” embryos that are “unavailable” because they are detected carrying certain genetic flaws. But there are still some embryos biopsied expected to have some genetic abnormality that might or not cause malfunction, including embryos with copy number variant of uncertain significance (VUS), embryos tested with adult-onset genetically anomalousness, embryos of balanced translocation as well as mosaic embryos. So how to dispose of this group of embryos in clinical practice is a hot issue up to now. In this debate, we reviewed the relevant case reports and original research combined with the joint consensus or committee opinion to state our proposition: embryos tested with possible abnormal genetic characteristics and thus expected to have mild adult disease should not be transferred. Parents undergoing PGT may wish to avoid the lifelong concern caused by the chance that their children may develop adult-onset conditions. The transfer of embryos expected to have mild adult disease is contrary to their original intention of seeking PGT treatment. Whether intentional or incidental, the discovery and request for transfer of embryos likely to result in the birth of offspring with health-affecting conditions pose ethical dilemmas for physicians and their staff, patients, and society. MOTION: AGAINST Preimplantation genetic testing provides couples with powerful reproductive choices. The technology allows individuals to avoid giving birth to children with significant health issues and developmental disability. Additionally, serious familial adult-onset conditions, such as predisposition to cancer or dementia, can be screened out of future generations. Polygenetic risk scores will be the next leap in genetic testing technology. This data can used to determine the chances of an embryo developing adult-onset conditions such as cardiovascular disease, diabetes, mental illness and even gout. This presentation argues that there is a limit at which society should stop screening embryos for disease and draws upon practical observations and well-accepted ethical frameworks to support the case.
Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 ...polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set ...included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis Pmeta = 7.55 × 10−21, odds ratio (OR) 0.71); 2p21 (rs13429458, Pmeta = 1.73 × 10−23, OR 0.67); and 9q33.3 (rs2479106, Pmeta = 8.12 × 10−19, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.
Embryonic development into an implantation-competent blastocyst, synchronized uterine transformation into a receptive stage, and an intimate cross-talk between the activated blastocyst and the ...receptive uterus are essential for successful implantation, and therefore for subsequent pregnancy outcome. Evidence accumulating during recent years has underlined the importance of the Wnt signaling pathway in mammalian implantation and decidualization. Herein, this review focuses on the current state of knowledge regarding Wnt signaling in multiple implantation and decidualization events: pre-implantation embryo development, blastocyst activation for implantation, uterine development, and decidualization.
Fat embolism syndrome (FES) is a common complication following long bone fracture; fat droplets are released into the blood circulation and form embolisms, mainly in lung and brain. However, the ...potential mechanisms involved remain to be clarified. In this study, the mechanism of brain injury following FES and the protective effects of urinary trypsin inhibitor (UTI)—a serine protease inhibitor—were investigated. Sixty male Sprague-Dawley rats were divided randomly into sham, FES and FES+UTI treatment groups. The FES model was established using tail vein injection of glycerol trioleate, and UTI was administered by intraperitoneal injection immediately following FES. Brain/lung water content evaluation, Evans blue content and magnetic resonance imaging examination were used to assess the effects of UTI. Furthermore, immunohistochemistry and western blot were also applied to explore the protective mechanism of UTI following FES. The results of oil red O staining indicated that the FES model was successfully established. UTI could significantly attenuate blood-brain-barrier (BBB) disruption, as seen through brain edema evaluation and Evans blue content examination. Immunofluorescence staining results indicated that the TLR4-JNK pathway was involved in brain injury after FES; this effect could be quenched by UTI treatment. Furthermore, UTI could decrease the levels of downstream target proteins of the TLR4-JNK pathway, phosphorylated-NF- κB (p65) and p53 in brain. Our results showed that UTI could alleviate BBB injury after FES through blocking activity of the TLR4-JNK pathway.
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