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1.
Angew Chem Int Ed Engl ; : e202215467, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36591974

RESUMO

Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability for US-triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX -PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX -PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS-STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX -PEG, the combination treatment of MoOX -triggered SDT and aCTLA-4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors.

2.
J Orthop Surg Res ; 17(1): 497, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36403073

RESUMO

OBJECTIVE: Currently, among wounds with large skin tissue defects caused by various reasons, the treatment of refractory wounds is still a major clinical problem. This study is aimed to preliminarily assess the therapeutic potentials of platelet-rich plasma (PRP) in refractory wounds with exposed tendons, as well as corresponding efficacy and safety. METHODS: A total of 12 patients (5 males and 7 females) with refractory wounds and exposed tendons who were admitted to our hospital from June 2018 to December 2020 were included in this study. After the preparation of PRP, the included patients underwent the PRP injection after the debridement of wounds, and the efficacy and prognosis were assessed by the same group of senior surgeons. RESULTS: The average age of included patients was 42.7 ± 12.9 years, and the causes of injury included traffic accidents (3 cases), contusion (2 cases), burns (2 cases), diabetes complications (4 cases), and melanoma complications (1 cases). The average healing time was 23.0 ± 5.0 days, and the mean size of the wound was 3.1 × 5.1 cm2. During the whole treatment process, Vancouver Scar Scale (VSS) decreased from 7.4 ± 1.6 before PRP treatment to 3.6 ± 0.9 after treatment (P < 0.001), Manchester Scar Scale (MSS) decreased from 12.3 ± 4.5 before PRP treatment to 5.4 ± 1.2 after treatment (P < 0.001), and no redness and swelling were observed around wounds, the size and degree of wounds gradually reduced, the coverage rate of granulation tissue was acceptable, overall quality of scar was relatively good, skin sensitivity around wounds was normal, there was no local wounds secretion, and postoperative patient's satisfaction was relatively good during follow-up. CONCLUSIONS: Our study has preliminarily indicated that PRP can promote the wounds healing, reduce the inflammation around wounds, and improve the granulation tissue and angiogenesis, thereby effectively polishing up the safety and efficacy.


Assuntos
Plasma Rico em Plaquetas , Traumatismos dos Tendões , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cicatriz , Cicatrização , Tendões
3.
Fertil Steril ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36404157

RESUMO

OBJECTIVE: To explore whether the associations of 3 blastocyst morphological parameters, namely, degree of blastocyst expansion (expansion), appearance of trophectoderm (TE) and inner cell mass, with live birth and singleton birth weight are influenced by blastocyst freezing and biopsy. DESIGN: A retrospective study. SETTING: An assisted reproductive technology center. PATIENT(S): 28,515 single blastocyst transfer cycles between January 2014 and August 2019. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Live birth and singleton birth weight. RESULT(S): Blastocyst transfer cycles were divided into 4 groups: biopsied blastocyst cycles (biopsied-blast), thawed blastocyst cycles (thawed-blast), blastocyst from thawed cleavage embryo cycles (blast-thawed-D3), and fresh blastocyst cycles (fresh-blast). Subgroup analyses by blastocyst stage (day 5 and day 6) were performed in thawed-blast and blast-thawed-D3. Because almost all blastocysts were biopsied on day 6 and fresh blastocysts were transferred on day 5, the biopsied-blast and fresh-blast were not divided into subgroups. First, the associations between blastocyst morphological parameters and live birth were analyzed. To explore the effect of freezing, we compared day-5 frozen cycles (thawed-blast) vs. day-5 fresh cycles (including fresh-blast and blast-thawed-D3) and day 6 frozen cycles (thawed-blast) vs. day-6 fresh cycles (blast-thawed-D3). Inner cell mass and TE were associated with live birth for day 5 embryos, and only TE affected live birth for day-6 embryos. The associations were the same in frozen cycles and fresh cycles. To explore the effect of biopsy, we compared day-6 biopsied cycles (biopsied-blast) vs. day-6 nonbiopsied cycles (including thawed-blast and blast-thawed-D3). All the 3 parameters were associated with live birth in biopsied-blast, whereas only TE was associated with live birth in nonbiopsied cycles. In addition, the associations between blastocyst morphological parameters and singleton birthweight were analyzed. In the 6 subgroups, expansion stage of day-6 embryos in biopsied-blast and TE grade of day-6 embryos in thawed-blast were associated with birth weight, and there are no associations in other subgroups. CONCLUSION(S): The association of blastocyst morphological parameters with live birth may be affected by blastocyst biopsy and/or genetic testing, and its association with birth weight may be affected by blastocyst freezing and biopsy and/or genetic testing.

4.
J Ultrasound Med ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394304

RESUMO

OBJECTIVES: To investigate the effectiveness of surgery for septate uterus in infertile patients before in vitro fertilization-embryo transfer (IVF-ET). METHODS: The data of 937 infertile patients with septate uterus and achieved singleton pregnancy after IVF-ET from January 2014 to December 2015 were retrospectively analyzed. Thousand five hundred seventy-eight infertile patients with a normal uterus who achieved singleton pregnancy during the same period were selected as the control group. Patients with septate uterus were divided into two groups according to whether the septum was resected. The pregnancy and perinatal outcomes of the surgical group and the nonsurgical group were compared with the control group. The secondary infertility patients who were surgically corrected septa were also chosen as self-controls and an analysis was performed on their fertility outcomes pre- and post-surgery. RESULTS: Compared with the control group, the surgical group had increased rates of early miscarriage, preterm delivery, and low birthweight and a significantly reduced live birth rate (P < .05). The outcomes of the nonsurgical and control groups were similar. Using secondary infertility patients who were surgically corrected septa as self-controls, after surgery, the rates of miscarriage and ectopic pregnancy were significantly lower and the live birth rate was significantly higher (P ≤ .001); however, perinatal mortality was not significantly different before and after surgery. CONCLUSIONS: Patients with a septum depth greater than 10 mm or 5-10 mm associated with a history of unexplained recurrent miscarriage, IVF failure, or infertility might benefit from resection of the uterine septum with hysteroscopic metroplasty.

5.
Phys Chem Chem Phys ; 24(46): 28530-28539, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36411969

RESUMO

Metal oxide sensors face the challenge of high response and fast recovery at low operating temperatures for the detection of toxic and flammable hydrogen sulfide (H2S) gases. Herein, novel In-doped ZnO with a sunflower-like structure and tunable surface properties was rationally synthesized. The substitutional In atom in the ZnO crystal can dramatically enhance the concentration of oxygen vacancies (Ov), the In-ZnO sites are responsible for fast recovery, and the formation of sub-stable sulfide intermediates gives rise to the high response towards H2S. As a result, the response of the optimized 4In-ZnO sensor is 3538.36 to 50 ppm H2S at a low operating temperature of 110 °C, which is 106 times higher than that of pristine ZnO. Moreover, the response time and recovery time to 50 ppm H2S are 100 s and 27 s, respectively, with high selectivity and stability. First-principles calculations revealed that 4In-ZnO with rich Ov exhibited higher adsorption energy for the H2S molecule than pristine ZnO, resulting in effortless H2S detection. Our work lays the foundation for the rational design of highly sensitive gas sensors through precise doping of atoms in oxygen-rich vacancies in semiconductor materials.

6.
Front Endocrinol (Lausanne) ; 13: 985741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339415

RESUMO

Study question: Is vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes? Study design size duration: This is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing and time-lapse monitoring of their embryos from August 2017 to September 2021. Main results: Embryo vacuolization on Days 3 and 4 is associated with the LH level on the day of the hCG trigger and the number of retrieved oocytes. Compared to vacuole-negative embryos, the rates of blastocyst formation and good-blastocyst formation was significantly lower in vacuole-positive embryos. We observed no significant difference in the rates of euploidy, implantation, ongoing pregnancy, and live birth between vacuole-positive and vacuole-negative embryos. In vacuole-positive embryos, the embryos of which the vacuole-positive blastomeres were involved in embryo compaction exhibited significantly higher mosaicism rate compared with those of which the vacuole-positive blastomeres were not involved in embryo compaction. Conclusion: Vacuolization in embryos on Days 3 and 4 is associated with reduced blastocyst formation rate and high-quality blastocyst rate. Blastocysts had a low mosaicism rate if the vacuole-containing cells were rejected in compaction process, which supports the hypothesis that exclusion of abnormal blastomeres from compaction is a self-correction mechanism.


Assuntos
Blastocisto , Técnicas de Cultura Embrionária , Gravidez , Feminino , Humanos , Técnicas de Cultura Embrionária/métodos , Estudos Retrospectivos , Desenvolvimento Embrionário/genética , Implantação do Embrião
7.
EMBO Mol Med ; 14(12): e16501, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36321563

RESUMO

Total fertilization failure (TFF) is an important cause of infertility; however, the genetic basis of TFF caused by male factors remains to be clarified. In this study, whole-exome sequencing was firstly used to screen for genetic causes of TFF after intracytoplasmic sperm injection (ICSI), and homozygous variants in the novel gene IQ motif-containing N (IQCN) were identified in two affected individuals with abnormal acrosome structures. Then, Iqcn-knockout mice were generated by CRISPR-Cas9 technology and showed that the knockout male mice resembled the human phenotypes. Additionally, we found that IQCN regulates microtubule nucleation during manchette assembly via calmodulin and related calmodulin-binding proteins, which resulted in head deformity with aberrant oocyte activation factor PLCζ. Fortunately, ICSI with assisted oocyte activation can overcome IQCN-associate TFF and male infertility. Thus, our study firstly identified the function of IQCN, highlights the relationship between the manchette assembly and fertilization, and provides a genetic marker and a therapeutic option for male-source TFF.

8.
Adv Healthc Mater ; : e2201771, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36226993

RESUMO

Wound microenvironment with excess reactive oxygen species (ROS) can significantly inhibit wound healing. Encouraged by hydrogen molecules (H2 ) with effective ROS scavenging and calcium hydride (CaH2 ) with sufficient H2 supply, the authors for the first time employed CaH2 as a therapeutic H2 donor and starch as a diluent to construct CaH2 pulvis dressing for wound healing treatment. It has been found that CaH2 by generating H2 exhibited excellent ROS scavenging performance, favorable for preserving the oxidative-stress-induced cell death. After being applied onto the skin wound, the CaH2 pulvis dressing with the unique ROS-scavenging ability can accelerate skin wound healing in healthy/diabetic mice (small animal models) and Bama mini-pigs (large animal model). Such CaH2 dressing can release H2 to relieve the inflammation levels, decrease the secretion of pro-inflammatory cytokines, increase the infiltration of inflammation-suppressive immune cells, and promote the regeneration of new blood vessels and collagens, thereby accelerating wound healing. This work highlighted that the integration of anti-oxidation and anti-inflammation functions based on CaH2 dressing endowed it with a promising possibility for the treatment of inflammatory diseases.

9.
Hum Reprod ; 37(11): 2546-2559, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36066440

RESUMO

STUDY QUESTION: Is there an efficient and cost-effective detection platform for different genetic conditions about embryos? SUMMARY ANSWER: A multifunctional haplotyping-based preimplantation genetic testing platform was provided for detecting different genetic conditions. WHAT IS KNOWN ALREADY: Genetic disease and chromosomal rearrangement have been known to significantly impact fertility and development. Therefore, preimplantation genetic testing for aneuploidy (PGT-A), monogenic disorders (PGT-M) and structural rearrangements (PGT-SR), a part of ART, has been presented together to minimize the fetal genetic risk and increase pregnancy rate. For patients or their families who are suffering from chromosome abnormality, monogenic disease, unexplained repeated spontaneous abortion or implantation failure, after accepting genetic counseling, they may be suggested to accept detection from more than one PGT platforms about the embryos to avoid some genetic diseases. However, PGT platforms work through different workflows. The high costliness, lack of material and long-time operation of combined PGT platforms limit their application. STUDY DESIGN, SIZE, DURATION: All 188 embryonic samples from 43 families were tested with HaploPGT platform, and most of their genetic abnormalities had been determined by different conventional PGT methods beforehand. Among them, there were 12 families only carrying structural rearrangements (115 embryos) in which 9 families accepted implantation and 5 families had normal labor ART outcomes, 7 families only carrying monogenic diseases (26 embryos) and 3 families carrying both structural rearrangements and monogenic diseases (26 embryos). Twelve monopronucleated zygotes (1PN) samples and 9 suspected triploid samples were collected from 21 families. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Here, we raised a comprehensive PGT method called HaploPGT, combining reduced representation genome sequencing, read-count analysis, B allele frequency and haplotyping analysis, to simultaneously detect different genetic disorders in one single test. MAIN RESULTS AND THE ROLE OF CHANCE: With 80 million reads (80M) genomic data, the proportion of windows (1 million base pairs (Mb)) containing two or more informative single nucleotide polymorphism (SNP) sites was 97.81%, meanwhile the genotyping error rate stabilized at a low level (2.19%). Furthermore, the informative SNPs were equally distributed across the genome, and whole-genomic haplotyping was established. Therefore, 80M was chosen to balance the cost and accuracy in HaploPGT. HaploPGT was able to identify abnormal embryos with triploid, global and partial loss of heterozygosity, and even to distinguish parental origin of copy number variation in mosaic and non-mosaic embryos. Besides, by retrospectively analyzing 188 embryonic samples from 43 families, HaploPGT revealed 100% concordance with the available results obtained from reference methods, including PGT-A, PGT-M, PGT-SR and PGT-HLA. LIMITATIONS, REASON FOR CAUTION: Despite the numerous benefits HaploPGT could bring, it still required additional family members to deduce the parental haplotype for identifying balanced translocation and monogenic mutation in tested embryos. In terms of PGT-SR, the additional family member could be a reference embryo with unbalanced translocation. For PGT-M, a proband was normally required. In both cases, genomic information from grandparents or parental siblings might help for haplotyping theoretically. Another restriction was that haploid, and diploid resulting from the duplication of a haploid, could not be told apart by HaploPGT, but it was able to recognize partial loss of heterozygosity in the embryonic genome. In addition, it should be noted that the location of rearrangement breakpoints and the situation of mutation sites were complicated, which meant that partial genetic disorders might not be completely detected. WIDER IMPLICATIONS OF THE FINDINGS: HaploPGT is an efficient and cost-effective detection platform with high clinical value for detecting genetic status. This platform could promote the application of PGT in ART, to increase pregnancy rate and decrease the birth of children with genetic diseases. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Natural Science Foundation of China (81873478, to L.H.), National Key R&D Program of China (2018YFC1003100, to L.H.), the Natural Science Foundation of Hunan Province (Grant 2022JJ30414, to P.X.), Hunan Provincial Grant for Innovative Province Construction (2019SK4012) and the Scientific Research Foundation of Reproductive and Genetic Hospital of China International Trust & Investment Corporation (CITIC)-Xiangya (YNXM-201910). Haplotyping analysis has been licensed to Basecare Co., Ltd. L.K., Y.M., K.K., D.Z., N.L., J.Z. and R.D. are Basecare Co., Ltd employees. The other authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Diagnóstico Pré-Implantação , Gravidez , Feminino , Criança , Humanos , Diagnóstico Pré-Implantação/métodos , Haplótipos , Estudos Retrospectivos , Triploidia , Variações do Número de Cópias de DNA , Testes Genéticos/métodos , Aneuploidia , Aberrações Cromossômicas
10.
J Transl Med ; 20(1): 396, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-36058949

RESUMO

BACKGROUND: Previous studies suggested that non-invasive preimplantation genetic testing (niPGT) for intracytoplasmic sperm injection (ICSI) blastocysts can be used to identify chromosomal ploidy and chromosomal abnormalities. Here, we report the feasibility and performance of niPGT for conventional in vitro fertilization (IVF) blastocysts. METHODS: This was a prospective observational study. In the preclinical stage, whole genome amplification and NGS were performed using the sperm spent culture medium (SCM). Then, trophectoderm (TE) biopsies and corresponding SCM derived from 27 conventional IVF monopronuclear embryos were collected. In the clinical stage, samples from 25 conventional IVF cycles and 37 ICSI cycles from April 2020-August 2021 were collected for performance evaluation. RESULTS: Preclinically, we confirmed failed sperm DNA amplification under the current amplification system. Subsequent niPGT from the 27 monopronuclear blastocysts showed 69.2% concordance with PGT results of corresponding TE biopsies. In the clinical stage, no paternal contamination was observed in any of the 161 SCM samples from conventional IVF. While maternal contamination was observed in 29.8% (48/161) SCM samples, only 2.5% (4/161) samples had a contamination ratio ≥ 50%. Compared with that of TE biopsy, the performances of NiPGT from 161 conventional IVF embryos and 122 ICSI embryos were not significantly different (P > 0.05), with ploidy concordance rates of 75% and 74.6% for IVF and ICSI methods, respectively. Finally, evaluation of the euploid probability of embryos with different types of niPGT results showed prediction probabilities of 82.8%, 77.8%, 62.5%, 50.0%, 40.9% and 18.4% for euploidy, sex-chromosome mosaics only, low-level mosaics, multiple abnormal chromosomes, high-level mosaics and aneuploidy, respectively. CONCLUSIONS: Our research results preliminarily confirm that the niPGT approach using SCM from conventional IVF has comparable performance with ICSI and might broadening the application scope of niPGT.


Assuntos
Diagnóstico Pré-Implantação , Blastocisto/patologia , Aberrações Cromossômicas , Meios de Cultura , Feminino , Fertilização In Vitro , Testes Genéticos/métodos , Humanos , Masculino , Gravidez , Diagnóstico Pré-Implantação/métodos , Sêmen
11.
Front Endocrinol (Lausanne) ; 13: 986848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105399

RESUMO

Background: Vitamin D plays an important role in reproduction. Evidence shown that free 25-hydroxyvitamin D (25(OH)VitD) was more accurate than total 25(OH)VitD in reflecting the status of 25(OH)VitD during pregnancy. However, the relationship between free 25(OH)VitD and female fertility parameters has not been reported yet. Therefore, this study aims to compare the correlation of free and total 25(OH)VitD with fertility parameters in infertility females undergoing in vitro fertilization and embryo transfer (IVF-ET) or intracytoplasmic sperm injection (ICSI). Methods: According to the inclusion and exclusion criteria, 2569 infertility patients who received IVF-ET or ICSI treatment for the first time participated in this study. Five milliliter peripheral blood samples of the patients were collected on the day before embryo transfer (ET). Enzyme linked immunosorbent assay (ELISA) kits was used to detect free 25(OH)VitD and total 25(OH)VitD, and clinical information was collected. Spearman's rho was used to evaluate the association between the variables. Results: The median (IQR) of free 25(OH)VitD was 4.71 (4.11-5.31) pg/mL and total 25(OH)VitD was 19.54 (16.52-22.83) ng/m. The correlation between them, however, was week (rho=0.311). Compared to total 25(OH)VitD, free 25(OH)VitD was slightly better correlated with basal follicle-stimulating hormone (FSH) (rho=0.041, P=0.036), basal estradiol (E2) (rho=0.089, P<0.001), anti-Müllerian hormone (AMH) (rho=-0.057, P=0.004), antral follicle count (AFC) (rho=-0.053, P=0.007), E2 (rho=-0.080, P<0.001), number of oocytes retrieval (rho=-0.079, P<0.001) and progesterone (P)/E2 on hCG trigger day (rho=0.081, P<0.001). Conclusions: Overall, there was only a rather weak correlation of free as well as total 25(OH)VitD with human endocrine and functional fertility parameters in women undergoing IVF/ICSI. Neither free nor total 25(OH)VitD seems to play a major role in human embryo implantation.


Assuntos
Infertilidade , Injeções de Esperma Intracitoplásmicas , Feminino , Fertilidade , Fertilização In Vitro , Humanos , Infertilidade/terapia , Masculino , Gravidez , Sêmen , Vitamina D , Vitaminas
12.
Genet Med ; 24(11): 2285-2295, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36107168

RESUMO

PURPOSE: This study aimed to investigate the spectrum and characteristics of segmental aneuploidies (SAs) of <10 megabase (Mb) length in human preimplantation blastocysts. METHODS: Preimplantation genetic testing for aneuploidy was performed in 15,411 blastocysts from 5171 patients using a validated 1 Mb resolution platform. The characteristics and spectrum of SAs, including the incidence, sizes, type, inheritance pattern, clinical significance, and embryo distribution, were studied. RESULTS: In total, 6.4% of the 15,411 blastocysts carried SAs of >10 Mb, 4.9% of embryos had SAs ranging between 1 to 10 Mb, and 84.3% of 1 to 10 Mb SAs were <5 Mb in size. Inheritance pattern analysis indicated that approximately 63.8% of 1 to 10 Mb SAs were inherited and were predominantly 1 to 3 Mb in size. Furthermore, 18.4% of inherited SAs and 51.9% de novo 1 to 10 Mb SAs were pathogenic or likely pathogenic (P/LP). Different from whole-chromosome aneuploidies, reanalysis indicated that 50% of the de novo 1 to 10 Mb SAs and 70% of the >10 Mb SAs arose from mitotic errors. CONCLUSION: Based on the established platform, 1 to 10 Mb SAs are common in blastocysts and include a subset of P/LP SAs. Inheritance pattern analysis and clinical interpretation based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines contributed to determine the P/LP SAs.


Assuntos
Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Aneuploidia , Blastocisto , Testes Genéticos
13.
Hum Reprod ; 37(11): 2578-2588, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36125002

RESUMO

STUDY QUESTION: Do differences in blood pressure within the normal range have any impacts on the live birth rate (primary outcome) or biochemical pregnancy rate (beta-hCG positivity), clinical pregnancy rate (heart beating in ultrasound), abortion rate and ectopic pregnancy rate (secondary outcomes) of fresh embryo transfer in women undergoing their IVF/ICSI treatment? SUMMARY ANSWER: Even rather small differences in baseline blood pressure in women with normal blood pressure according to current guidelines undergoing fresh embryo transfer after IVF/ICSI affects substantially the live birth rate. WHAT IS KNOWN ALREADY: Pre-pregnancy hypertension is a well-known risk factor for adverse pregnancy events such as preeclampsia, fetal growth restriction, placental abruption and adverse neonatal events. It is likewise well known that hypertension during pregnancy in women undergoing ART is associated with adverse pregnancy outcomes. However, whether blood pressure at the high end of the normal range has an impact on ART is unknown. STUDY DESIGN, SIZE, DURATION: It is a prospective observational cohort study based on a single IVF center between January 2017 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two thousand four hundred and eighteen women with normal blood pressure undergoing fresh embryo transfer after IVF/ICSI at the Reproductive and Genetic Hospital of CITIC-Xiangya were enrolled in this study. MAIN RESULTS AND THE ROLE OF CHANCE: Blood pressure was measured at the first visit when women consulted the IVF center due to infertility. In women with a successful pregnancy outcome (1487 live births out of 2418 women undergoing fresh embryo transfer after IVF/ICSI), systolic blood pressure (SBP) (114.1 ± 9.48 mmHg versus 115.4 ± 9.8 mmHg, P = 0.001) and diastolic blood pressure (DBP) (74.5 ± 7.5 mmHg versus 75.3 ± 7.34 mmHg, P = 0.006) were lower than in those who did not achieve live births. Multivariate logistic regression analysis revealed that SBP (OR: 0.987, 95% CI: 0.979-0.996, P = 0.004) and DBP (OR: 0.986, 95% CI: 0.975-0.998, P = 0.016) were negatively associated with live birth. Similarly, SBP was significantly negatively related to clinical pregnancy rate (OR: 0.990, 95% CI: 0.981-0.999, P = 0.033), while for DBP the association was not statistically significant (OR: 0.994, 95% CI: 0.982-1.006, P = 0.343). However, both SBP and DBP were positively associated with miscarriage OR: 1.021 (95% CI: 1.004-1.037, P = 0.013) and OR: 1.027 (95% CI: 1.005-1.049, P = 0.014), respectively. Both SBP and DBP were unrelated to biochemical pregnancy (hCG positivity), implantation and ectopic pregnancy rate. LIMITATIONS, REASONS FOR CAUTION: Whether lowering blood pressure before initiating ART treatment in women with SBP or DBP higher than the thresholds defined in our study will confer a benefit is unknown. Also, we cannot exclude bias due to different ethnicities. Moreover, participants in our study only received fresh embryo transfer, whether the results could apply to frozen embryo transfer is unclear. WIDER IMPLICATIONS OF THE FINDINGS: Our study challenges the current blood pressure goals in women undergoing fresh embryo transfer after IVF/ICSI. Further studies are needed to figure out the mechanism and effective approach to increase IVF/ICSI pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): Hunan Provincial Grant for Innovative Province Construction (2019SK4012). The authors declare that there were no conflicts of interest in this study. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Hipertensão , Gravidez Ectópica , Recém-Nascido , Feminino , Gravidez , Humanos , Coeficiente de Natalidade , Injeções de Esperma Intracitoplásmicas/métodos , Estudos Prospectivos , Pressão Sanguínea , Estudos Retrospectivos , Placenta , Transferência Embrionária/métodos
14.
J Ultrasound Med ; 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36173144

RESUMO

OBJECTIVES: What is the role of transvaginal sonography (TVS) in the early diagnosis of hectopic interstitial pregnancy (HIP) after in vitro fertilization-embryo transfer (IVF-ET)? METHODS: A retrospective observational study was conducted from January 2005 to December 2018. Routine two-dimensional and three-dimensional TVS were used to confirm clinical pregnancy. Women were diagnosed with HIP when an intrauterine gestational sac was combined with an extrauterine chorionic sac, which was at least 1 cm away from the uterine cavity and surrounded by a thin myometrial layer (<5 mm). Surgery and pathology results were the gold standard for diagnosing interstitial pregnancy. Non-surgical patients were excluded from the study. The performance of TVS and the pregnancy outcomes of intrauterine pregnancies (IUPs) were evaluated. RESULTS: A total of 97,161 women underwent IVF treatment and TVS examinations in our hospital during this study. Of these, 194 patients were diagnosed with HIP, with an incidence of 0.2% (194/97,161). Surgical and pathological findings confirmed 179 interstitial pregnancies, of which 174 were diagnosed by TVS, 4 were missed, and 1 was misdiagnosed. The sensitivity of TVS diagnosis was 97.8% and the positive predictive value was 99.4%. The mean time to diagnosis was 31 days after transplantation. One hundred and thirty-nine cases of HIP (77.7%) were diagnosed at the time of initial TVS examination. In 132 patients (73.7%), IUPs resulted in live births. CONCLUSIONS: In our practice, most HIPs following IVF-ET can be accurately diagnosed by TVS, which facilitates early management of interstitial pregnancies and enables high live birth rates for IUPs.

15.
ACS Nano ; 16(10): 17242-17256, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36170351

RESUMO

The further bioapplications of sonodynamic therapy (SDT) were hindered by the inadequate efficiency and poor degradability of sonosensitizers and the hypoxic tumor microenvironment (TME). Therefore, it is ideal to develop pH-sensitive sonosensitizers that generate abundant reactive oxygen species (ROS) and rapidly degrade in a neutral environment while slowly degrading in an acidic environment to reduce their long-term toxicity. Herein, the defective tungsten oxide nanobelts (WOx NBs) were developed as a type of pH-sensitive and biodegradable sonosensitizers with a high SDT efficiency and low toxicity for enhanced SDT. The defective oxygen sites of WOx NBs could inhibit the recombination of electrons and holes, making WOx NBs promising sonosensitizers that could generate abundant ROS under ultrasound (US) irradiation. Enhanced by the catalase (CAT) that reacted with H2O2 to generate O2, the WOx NBs exhibited better SDT performance against 4T1 cells in both normoxic and hypoxic environments. In addition, the WOx NBs could degrade by releasing protons (H+), resulting in intracellular acidification and inhibited cell motility that further enhanced the therapeutic effects of SDT. Assisted with CAT and ALG for hypoxia refinement and better retention, the WOx NBs enabled effective SDT and antimetastasis against 4T1 tumors in vivo. Most importantly, the WOx NBs could degrade rapidly in normal tissues but slowly in an acidic TME, which was favorable for their fast clearance, without any obvious long-term toxicity. Our work developed defective WOx NBs with a high SDT efficiency and pH-sensitive degradation for enhanced SDT, which extended the biomedical application of tungsten-based nanomaterials and the further development of SDT.


Assuntos
Neoplasias , Terapia por Ultrassom , Humanos , Tungstênio , Espécies Reativas de Oxigênio/metabolismo , Catalase , Oxigênio , Prótons , Peróxido de Hidrogênio , Neoplasias/terapia , Neoplasias/patologia , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Microambiente Tumoral
16.
Reprod Biol Endocrinol ; 20(1): 127, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996188

RESUMO

OBJECTIVE: To examine the effects and mechanisms of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization (IVF)-embryo transfer (ET). DESIGN, SETTING, AND PARTICIPANTS: This efficacy study was a multicenter, randomized, controlled clinical trial (RCT) in women receiving IVF-ET. The mechanistic study was a single-center RCT. INTERVENTIONS: The participants received TEAS vs. no TEAS treatment. MAIN OUTCOME MEASURES: In the efficacy study, the primary outcomes were the rates of clinical pregnancy, embryo implantation, and live birth. In the mechanistic study, sex hormones and endometrial protein expression were examined. RESULTS: Ultimately, 739 participants were enrolled (367 and 372 in the TEAS and control groups, respectively). The clinical pregnancy rate was higher in the TEAS group than in the controls (55.1% vs. 46.7%, P = 0.03). There were no significant differences in embryo implantation, biochemical pregnancy, and live birth rates between the two groups (all P > 0.05) in the study population. In women > 35 years, the clinical pregnancy rates, embryo implantation rates and live birth rates in the TEAS and control groups were 48.9% vs. 23.7% (P = 0.004),30.8 vs. 13.9% (P = 0.001) and 34.0% vs. 19.7% (P = 0.06) respectively. In the mechanistic study with 120 participants, on the theoretical embryo implantation day, better developed endometrial pinopodes, elevated endometrial integrin α1ß1/αVß3, leukemia inhibitory factor, and elevated serum progesterone levels were found in the TEAS group compared with controls. CONCLUSION: TEAS significantly improved the clinical pregnancy rate in women undergoing IVF-ET, especially in women of older age. It might be due to improved endometrial receptivity. TRIAL REGISTRATION: ChiCTR-TRC-13003950.


Assuntos
Pontos de Acupuntura , Resultado da Gravidez , Idoso , Transferência Embrionária/métodos , Feminino , Fertilização In Vitro/métodos , Humanos , Gravidez , Taxa de Gravidez , Resultado do Tratamento
17.
Reprod Biomed Online ; 45(4): 721-726, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35989167

RESUMO

RESEARCH QUESTION: Do differences exist in euploidy rates in preimplantation genetic testing for aneuploidy (PGT-A) cycles with oral dydrogesterone primed ovarian stimulation protocol or the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol? DESIGN: A retrospective cohort study. Patients received the oral dydrogesterone or the GnRH antagonist in the first PGT-A cycle between November 2017 and May 2019. Propensity matching was used to identify a propensity-matched antagonist group based on age, BMI and AMH with a 1:1 ratio. The primary outcome was the rate of euploid embryos. RESULTS: A total of 780 cycles were included, consisting of 390 cycles receiving dydrogesterone and 390 cycles receiving GnRH antagonist protocol. No significant difference was found in patient baseline and cycle characteristics in the two groups. No statistical difference was found in the number of oocytes retrieved, metaphase II oocytes, embryos biopsied and embryo testing between the two groups. As no biopsy blastocysts formed in some cycles, only 262 cycles in the study group and 263 cycles in the antagonist group received next-generation sequencing testing, respectively. Similar to our overall data, the euploid rate per embryo biopsied was not significantly different. No significant differences were found between the two groups after stratifying by age and controlling for PGT-A testing modality. CONCLUSIONS: Ovulation inhibition by exogenous progestins in ovarian stimulation cycles should, therefore, be considered a valid modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement.


Assuntos
Didrogesterona , Diagnóstico Pré-Implantação , Aneuploidia , Feminino , Fertilização In Vitro/métodos , Testes Genéticos/métodos , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios , Humanos , Indução da Ovulação/métodos , Gravidez , Diagnóstico Pré-Implantação/métodos , Progestinas , Estudos Retrospectivos
18.
Angew Chem Int Ed Engl ; 61(39): e202208849, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-35929496

RESUMO

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)-mediated cancer therapy. Herein, vanadium-based nanocatalysts, hydrogen vanadium bronzes (HX V2 O5 , for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi-functional catalytic activity in decomposing H2 O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS-mediated cancer therapies.


Assuntos
Neoplasias , Vanádio , Linhagem Celular Tumoral , Glutationa/metabolismo , Humanos , Hidrogênio , Neoplasias/terapia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
19.
Adv Sci (Weinh) ; 9(30): e2201069, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36026580

RESUMO

Gas-mediated sonodynamic therapy (SDT) has the potential to become an effective strategy to improve the therapeutic outcome and survival rate of cancer patients. Herein, titanium sulfide nanosheets (TiSX NSs) are prepared as cascade bioreactors for sequential gas-sonodynamic cancer therapy. TiSX NSs themselves as hydrogen sulfide (H2 S) donors can burst release H2 S gas. Following H2 S generation, TiSX NSs are gradually degraded to become S-defective and partly oxidized into TiOX on their surface, which endows TiSX NSs with high sonodynamic properties under ultrasound (US) irradiation. In vitro and in vivo experiments show the excellent therapeutic effects of TiSX NSs. In detail, large amounts of H2 S gas and reactive oxygen species (ROS) can simultaneously inhibit mitochondrial respiration and ATP synthesis, leading to cancer cell apoptosis. Of note, H2 S gas also plays important roles in modulating and activating the immune system to effectively inhibit pulmonary metastasis. Finally, the metabolizable TiSX NSs are excreted out of the body without inducing any significant long-term toxicity. Collectively, this work establishes a cascade bioreactor of TiSX NSs with satisfactory H2 S release ability and excellent ROS generation properties under US irradiation for programmed gas-sonodynamic cancer therapy.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Reatores Biológicos , Trifosfato de Adenosina
20.
Front Endocrinol (Lausanne) ; 13: 920973, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846284

RESUMO

Objective: To date, evidence regarding the effectiveness and safety of two consecutive cycles of single embryo transfer (2SETs) compared with one cycle of double embryo transfer (DET) has been inadequate, particularly considering infertile women with different prognostic factors. This study aimed to comprehensively summarize the evidence by comparing 2SETs with DET. Methods: PubMed, Embase, Cochrane Library databases, ClinicalTrails.gov, and the WHO International Clinical Trials Registry Platform were searched up to March 22, 2022. Peer-reviewed, English-language randomized controlled trials (RCTs) and observational studies (OS) comparing the outcomes of 2SETs with DET in infertile women with their own oocytes and embryos were included. Two authors independently conducted study selection, data extraction, and bias assessment. The Mantel-Haenszel random-effects model was used for pooling RCTs, and a Bayesian design-adjusted model was conducted to synthesize the results from both RCTs and OS. Main Results: Twelve studies were finally included. Compared with the DET, 2SETs were associated with a similar cumulative live birth rate (LBR; 48.24% vs. 48.91%; OR, 0.97; 95% credible interval (CrI), 0.89-1.13, τ2 = 0.1796; four RCTs and six observational studies; 197,968 women) and a notable lower cumulative multiple birth rate (MBR; 0.87% vs. 17.72%; OR, 0.05; 95% CrI, 0.02-0.10, τ2 = 0.1036; four RCTs and five observational studies; 197,804 women). Subgroup analyses revealed a significant increase in cumulative LBR (OR, 1.33; 95% CrI, 1.29-1.38, τ2 = 0) after two consecutive cycles of single blastocyst transfer compared with one cycle of double blastocyst transfer. Moreover, a lower risk of cesarean section, antepartum hemorrhage, preterm birth, low birth weight, and neonatal intensive care unit admission but a higher gestational age at birth and birth weight were found in the 2SETs group. Conclusion: Compared to the DET strategy, 2SETs result in a similar LBR while simultaneously reducing the MBR and improving maternal and neonatal adverse outcomes. The 2SETs strategy appears to be especially beneficial for women aged ≤35 years and for blastocyst transfers.


Assuntos
Transferência Embrionária , Peso ao Nascer , Transferência Embrionária/métodos , Feminino , Humanos , Gravidez , Taxa de Gravidez , Transferência de Embrião Único
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