A predictive model for first-trimester pregnancy inception after IVF-ET based on multimodal ultrasound evaluation of endometrial receptivity.

BACKGROUND: In-vitro fertilization-embryo transfer (IVF-ET) is a commonly used assisted reproductive technology. Its success depends on many factors, including endometrial receptivity. Endometrial receptivity can be evaluated by ultrasound, endometrial biopsy, and magnetic resonance imaging. Compared with the latter two methods, ultrasound has the advantages of wide availability, non-invasiveness, and low cost. Three-dimensional (3D) ultrasound imaging examines endometrial thickness, morphology, and blood vessels, which are associated with the success of embryo implantation. However, there are no reports of endometrial receptivity assessment by 3D ultrasound. Therefore, we aimed to evaluate endometrial receptivity using 3D ultrasound and construct a predictive model for first-trimester pregnancy inception following IVF-ET. METHODS: We performed a prospective observational study on infertile women who underwent IVF-ET between December 2019 and February 2021. These women had 3D ultrasound evaluations, measuring endometrial thickness, volume, pattern, morphology, peristalsis, uterine artery blood flow index, sub-endometrial blood flow index, and distribution pattern. We recorded the occurrence of first-trimester pregnancies in these women. Using Akaike information criterion (AIC) and backward stepwise regression, a first-trimester pregnancy prediction model was constructed based on the minimum AIC value and validated internally and externally. RESULTS: 111 women were enrolled, with 103 included in the analysis. Univariate and multiple logistic regression analyses showed that endometrial thickness and vascularization flow index (VFI) were independent factors associated with the occurrence of a pregnancy. The final prediction model corresponding to the minimum AIC value (65.166) was Y = - 6.131-0.182endometrial thickness + 0.542endometrial volume + 4.374VFI + 0.132age. In the test set, modeling cohort, and external validation cohort, the model showed satisfactory differentiation, with C index of 0.841 (95%CI 0.699-0.817), 0.727 (95%CI 0.619-0.815), and 0.745 (95%CI 0.671-0.840), respectively. The Hosmer-Lemeshow goodness of fit tests reported P = 0.865, 0.139, and 0.070, respectively, indicating a high agreement with the actual IVF-ET outcome. This model reached the highest diagnostic efficiency (sensitivity 88.9%, specificity 75%, Youden index 0.639) at a diagnostic cut-off value of ≥ 0.360. CONCLUSIONS: The predictive model based on endometrial receptivity evaluations by 3D ultrasound had high diagnostic efficiency and could be a simple and effective tool to predict first-trimester pregnancy inception after IVF-ET.

The Effect of Human Umbilical Cord Mesenchymal Stem Cell on Premature Ovarian Cell Senilism Through miR-10a.

Objective: To investigate the potential protective impact of miR-10a-modified HUMSCs-derived exosomes on both premature ovarian failure and the functionality of ovarian granulosa cells in a POF model. Methods: KGN cells were co-cultured with cisplatin-diaminedichloroplatinum (II) (10 µM) for 24 h to establish an in vitro POF model. The cells were distributed into three distinct groups: the control group, the POF group, and the POF + HUCMSC group. The plasmid sh-NC, sh-miR-10 a and miR-10 a mimic were transfected into KGN cells. After co-cultured with HUCMSC-EVs for 48 h, they were divided into HUCMSC group, sh-miR-10 a-HUMSCs-exosomes group and miR-10 a-HUMSCs-exosomes group. Flow cytometry was adopted to assess the impact of HUMSCs surface immune antigens and miR-10a-HUCMSCs-exosomes on KGN cell apoptosis. Additionally, the evaluation of cell proliferation was carried out through CCK-8 and EDU assays. Western blot analysis was utilized to detect the Caspase-3, Bax, and Bcl-2 proteins levels. Furthermore, the levels of TNF-α, IL-6, IL-10, MDA, SOD, and CAT were quantified using ELISA. Results: Compared with the Control group, the POF group inhibited the growth of ovarian granulosa cells (P<0.01), reduced the number of EDU cells (P<0.01), and increased the protein expression of Caspase-3 (P<0.05) and Bax (P<0.01). HUMSCs treatment significantly down-regulated the expression of IL-6, TNF-α and MDA, while up-regulating the expression of IL-10, SOD and CAT (P<0.01); the overexpression of miR-10a promoted cell growth, besides, the introduction of miR-10a-HUMSCs-derived exosomes led to an elevation in the proliferation rate of OGCs affected by POF and concurrently suppressed the apoptosis rate. Conclusion: HUMSCs-derived exosomes modified by miR-10a have protective effects on premature ovarian failure and ovarian granulosa cell function in POF model.

The changes of Th17 cells and the related cytokines in the progression of human colorectal cancers.

BACKGROUND: The role of Th17 cells in colorectal tumorigenesis and development still remains unclear, despite the fact that it has been established in the pathogenesis of autoimmune diseases. METHODS: We first analyzed Th17 cells and Treg cells using flow cytometry in the circulation of colorectal adenoma (CRA) and colorectal carcinoma (CRC) patients and healthy controls, and the frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) stimulated by anti-CD3 plus anti-CD28 and treated by IL-1ß, IL-6, and TGF-ß in different concentrations. We then detected cytokines IL-1ß, IL-6, IL-17A, IL-21, IL-23 or TGF-ß by ELISA in sera and supernatants from both normal and tumor tissues cultured ex vivo. RESULTS: It was found that the percentage of Th17 and Treg cells increased in the circulation of both CRA and CRC patients; the increase of Th17 cells in the circulation occurred in early stages, whereas the increase of Treg cells in the circulation and the increase of Th17 cells in tumor tissues occurred in advanced stages. The subsequent cytokine profiling showed that, along CRC progression, IL-1ß, IL-17A and IL-23 underwent a similar change, while IL-6 in CRC exhibited an opposite change, with Th17 cells. In addition, high levels of TGF-ß and IL-17A were detected in tumor tissues rather than in normal mucosa. The in vitro experiment further demonstrated that IL-1ß, IL-6 or TGF-ß modulated Th17 cell expansion in PBMC. CONCLUSIONS: Our study reveals a unique change of Th17 cells, which is regulated possibly by IL-1ß, IL-6 and TGF-ß in the progression of CRC.

Quantum Monte Carlo calculated potential energy curve for the helium dimer.

We report on the results of both the diffusion quantum Monte Carlo (DMC) and reptation quantum Monte Carlo (RMC) methods on the potential energy curve of the helium dimer. We show that it is possible to obtain a highly accurate description of the helium dimer. An improved stochastic reconfiguration technique is employed to optimize the many-body wave function, which is the starting point for highly accurate simulations based on the DMC and RMC methods. We find that the results of these methods are in excellent agreement with the best theoretical results at short range, especially the recently developed RMC method, yield particularly accurate results with reduced statistical error, which gives very excellent agreement across the whole potential curve. For the equilibrium internuclear distance of 5.6 bohrs, the calculated total energy with RMC method is -5.807 483 599+/-0.000 000 016 hartree and the corresponding well depth is -11.003+/-0.005 K.

[Osteonecrosis of the jaw associated with the use of bisphosphonates in multiple myeloma: report of four cases and literature review].

OBJECTIVE: To summarize the clinical features of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients treated with bisphosphonate. METHODS: The clinical data of 4 patients with bisphosphonate-related (ONJ) in MM were reported and literatures were reviewed. RESULTS: In these patients, 3 males and 1 female, aged 59-73, pamidronate combined with chemotherapy, high dose glucocorticosteroid, and anti-angiogenic drug had been used for 12-44 months before the occurrence of ONJ. In treatment of ONJ conservative debridement of necrotic bone, systematic use of antibiotics, use of chlorhexidine acetate gargle, and withdrawal of bisphosphonates were preferable to aggressive surgical measures. CONCLUSION: Long-term use of bisphosphonates combined with chemotherapy in MM may cause ONJ that involves both mandible and maxilla. No satisfactory therapy is currently available.

Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice.

We describe the effects of the overexpression of noggin, a bone morphogenetic protein (BMP) inhibitor, on osteoblast differentiation and bone formation. Cells of the osteoblast and chondrocyte lineages, as well as bone marrow macrophages, showed intense beta-gal histo- or cytostaining in adult noggin+/- mice that had a LacZ transgene inserted at the site of noggin deletion. Despite identical BMP levels, however, osteoblasts of 20-month-old C57BL/6J and 4-month-old senescence-accelerated mice (SAM-P6 mice) had noggin expression levels that were approximately fourfold higher than those of 4-month-old C57BL/6J and SAM-R1 (control) mice, respectively. U-33 preosteoblastic cells overexpressing the noggin gene showed defective maturation and, in parallel, a decreased expression of Runx-2, bone sialoprotein, osteocalcin, and RANK-L. Noggin did not inhibit the ligandless signaling and pro-differentiation action of the constitutively activated BMP receptor type 1A, ca-ALK-3. Transgenic mice overexpressing noggin in mature osteocalcin-positive osteoblasts showed dramatic decreases in bone mineral density and bone formation rates with histological evidence of decreased trabecular bone and CFU-osteoblast colonies at 4 and 8 months. Together, the results provide compelling evidence that noggin, expressed in mature osteoblasts, inhibits osteoblast differentiation and bone formation. Thus, the overproduction of noggin during biological aging may result in impaired osteoblast formation and function and hence, net bone loss.

Effect of culture conditions on metabolites produced by the crinoid-derived fungus Aspergillus ruber 1017.

Two different culture media were used to cultivate fungus Aspergillus ruber 1017 and resulted in the isolation of one new compound (1) and 23 known compounds (2-24). Alkaloids were the major metabolite in soybean medium instead of anthraquinone from rice medium. The structures of these compounds were elucidated according to spectroscopic analysis and comparison with reported data. Antibacterial activities of compounds 1-12 against 12 aquatic bacteria were evaluated.

Disordered osteoclast formation and function in a CD38 (ADP-ribosyl cyclase)-deficient mouse establishes an essential role for CD38 in bone resorption.

We have evaluated the role of the ADP-ribosyl cyclase, CD38, in bone remodeling, a process by which the skeleton is being renewed constantly through the coordinated activity of osteoclasts and osteoblasts. CD38 catalyzes the cyclization of its substrate, NAD+, to the Ca2+-releasing second messenger, cyclic ADP-ribose (cADPr). We have shown previously that CD38 is expressed both in osteoblasts and osteoclasts. Its activation in the osteoclast triggers Ca2+ release through ryanodine receptors (RyRs), stimulation of interleukin-6 (IL-6), and an inhibition of bone resorption. Here, we have examined the consequences of deleting the CD38 gene in mice on skeletal remodeling. We report that CD38-/- mice displayed a markedly reduced bone mineral density (BMD) at the femur, tibia, and lumbar spine at 3 months and at the lumbar spine at 4 months, with full normalization of the BMD at all sites at 5 months. The osteoporosis at 3 months was accompanied by a reduction in primary spongiosa and increased osteoclast surfaces on histomorphometric analysis. Hematopoetic stem cells isolated ex vivo from CD38-/- mice showed a dramatic approximately fourfold increase in osteoclast formation in response to incubation for 6 days with RANK-L and M-CSF. The osteoclasts so formed in these cultures showed a approximately 2.5-fold increase in resorptive activity compared with wild-type cells. However, when adherent bone marrow stromal cells were allowed to mature into alkaline phosphatase-positive colony-forming units (CFU-Fs), those derived from CD38-/- mice showed a significant reduction in differentiation compared with wild-type cells. Real-time RT-PCR on mRNA isolated from osteoclasts at day 6 showed a significant reduction in IL-6 and IL-6 receptor mRNA, together with significant decreases in the expression of all calcineurin A isoforms, alpha, beta, and gamma. These findings establish a critical role for CD38 in osteoclast formation and bone resorption. We speculate that CD38 functions as a cellular NAD+ "sensor," particularly during periods of active motility and secretion.

[Screening of prognostic factors and comparing of staging systems of multiple myeloma].

This study was aimed to investigate the clinical features and laboratory data of 56 patients with multiple myeloma (MM), find the potential prognostic factors and compare Durie Salmon staging system with International Staging System for patients classification. The median survival time was calculated by the Kaplan Meier, and survival curves were compared using the Log-Rank test. Potential prognostic factors were evaluated by univariate and multivariate analyses. Bivariate correlation of Durie Salmon staging system with International Staging System were analyzed. The results showed that the median survival time of the patients was 42.7 months. Prognostic factors identified as adversely affecting survival included low levels of hemoglobin, platelet, serum albumin, high levels of lactate dehydrogenase, creatinine, C-reactive, serum ß2-microglobulin and high proportion of plasma cells in bone marrow. Among them, only hemoglobin level had independent prognostic value in MM. Durie Salmon staging system significantly correlated with International Staging System. In DS staging system, significant survival differences were found between patients in stages I and III, but statistically significant survival differences were observed among the all three stages in International Staging System. It is concluded that hemoglobin, platelet, serum albumin, lactate dehydrogenase, creatinine, C-reactive, ß2-microglobulin and the number of plasma cells in bone marrow have clinical value for evaluating the prognosis of MM patients. International Staging System can significantly distinguish three clinical stages of MM patients.