Successful pregnancy and delivery after premature ovarian insufficiency combined with undifferentiated connective tissue disease: a case report.

BACKGROUND: Premature ovarian insufficiency (POI) is extremely rare in the early stage of undifferentiated connective tissue disease. Patients with POI find it difficult to achieve successful pregnancy and delivery. CASE PRESENTATION: A 27-year-old female visited an outpatient department for premature ovarian insufficiency (POI) and infertility. She had regular menstrual periods since she was 14 years old and had no history of systemic disease. Laboratory tests showed low estrogen (15 ng/L, range 19.6-144.2 ng/L), elevated follicle-stimulating hormone (34 U/L), low anti-Mullerian hormone (0.1 µg/L), normal prolactin (11.48 ng/mL), and thyroid stimulating hormone (TSH) levels (0.97 mU/L). She demonstrated smaller bilateral ovarian volume and positivity to antinuclear and antiphospholipid antibodies. After the failure of conventional drug therapy and in vitro fertilization, the patient became pregnant naturally after treatment with glucocorticoids. CONCLUSION: Immunosuppression could help improve ovarian function and pregnancy outcomes in POI patients, but the therapeutic mechanisms are not clear and should be elucidated with more clinical studies.

A procedure for producing an anti-AXL nanobody in E. coli.

As one of the receptors of the TAM family, AXL plays a vital role in stem cell maintenance, angiogenesis, immune escape of viruses and drug resistance against tumors. In this study, the truncated extracellular segment containing two immunoglobulin-like domains of human AXL (AXL-IG), which has been confirmed to bind growth arrest specific 6 (GAS6) by structural studies [1], was expressed in a prokaryotic expression system and then purified. Immunizing camelid with the purified AXL-IG as antigen could lead to the production of unique nanobodies composed of only variable domain of heavy chain of heavy-chain antibody (VHH), which are around 15 kD and stable. We screened out a nanobody A-LY01 specific binding to AXL-IG. We further determined the affinity of A-LY01 to AXL-IG and revealed that A-LY01 could specifically recognize full-length AXL on the surface of HEK 293T/17 cells. Our study provides appropriate support for the development of diagnostic reagents and antibody therapeutics targeting AXL.

[Effect of single basal application of controlled-release blended fertilizer on reactive nitrogen loss, carbon and nitrogen footprint during summer maize growth period]. / 基施控释掺混肥对夏玉米生长期活性氮损失和碳氮足迹的影响.

To elucidate the agronomic and environmental effects of single basal application of controlled-release blended fertilizer in summer maize, and optimize management measures of nitrogen fertilizer for grain production in North China Plain, we conducted a field experiment in Dezhou Modern Agricultural Science and Technology Park in Shandong Province. There were four treatments: CK (no N fertilizer), FFP (farmer's fertilizing practice, 240 kg N·hm-2), OPT (optimized nitrogen application, 210 kg N·hm-2), and CRBF (controlled-release blended fertilizer with single basal application, 210 kg N·hm-2). We compared maize yield and reactive nitrogen loss, and quantitatively evaluated the carbon and nitrogen footprints by using life cycle assessment method. The results showed that nitrogen application significantly increased summer maize yield. Compared with FFP, OPT and CRBF increased summer corn yield by 0.7% and 2.9%, respectively, decreased the total amount of ammonia volatilization, N2O emission, and nitrate leaching by 13.0% and 72.7%, 13.3% and 37.5%, 20.5% and 23.5% respectively. Compared with CK, nitrogen application significantly increased the global warming potential (GWP) of summer maize production. Compared with FFP, GWP and greenhouse gas emission intensity of OPT decreased by 3.8% and 4.2%, while the reduction of CRBF were 8.7% and 12.0%, respectively. Compared with CK, nitrogen application significantly increased the carbon and nitrogen footprint of summer maize production. The production and transportation of nitrogen fertilizer and soil greenhouse gas emission were the main contributing factors of the carbon footprint, with contribution rates of 54%-60% and 24%-31%, respectively. Nitrate leaching was the main contributing factor of nitrogen footprint, with contribution rate of 57%-94%. Compared with FFP, the carbon and nitrogen footprints of OPT and CRBF were reduced by 11.0% and 16.5%, 19.6% and 28.4%, respectively. Considering the yield, reactive nitrogen loss and carbon and nitrogen footprint, we recommended the single basal application of controlled-release blended fertilizer as an effective nitrogen fertilizer management measure to promote grain clean production in the North China Plain.

Effect of Ezrin on regulating trophoblast cell invasion via PKC signaling pathway in unexplained recurrent spontaneous abortion.

Trophoblast cells are the most important cells in early pregnancy and their invasion are essential to the establishment and maintenance of pregnancy. Inadequate trophoblast cell invasion has been closely associated with several pregnancy-associated diseases including recurrent spontaneous abortion (RSA). Ezrin is an actin-associated protein, known as a marker for carcinogenesis and metastasis in solid tumors, has been proposed to play a role in the formation of microvilli in the early embryo. To further characterize its function in early pregnancy, we explored the expression of Ezrin in the trophoblast cells in early pregnancy. In this study, compared with normal pregnant women, we demonstrated that the expression of Ezrin and phosphorylated Ezrin decreased in the trophoblast cells in unexplained RSA (URSA) patients, and knockdown of Ezrin expression could suppress the invasiveness of trophoblast cells significantly. Various studies indicated that the phosphorylation of Ezrin on C-terminal threonine residue (T567) is a key event in the regulation of its activity. Our further exploration indicated that Ezrin was activated via PKC pathway. Furthermore, inhibition of the PKC pathway by a specific inhibitor suppressed invasiveness of Bewo cells. On the other hand, activation of the PKC pathway could increase the relative capacity of trophoblast cell invasion, while Ezrin knockdown reversed PKC activation induced cell invasion. These findings might provide a new fundamental mechanism for successful pregnancy and new diagnostic and therapeutic target for RSA.

Long Non-Coding RNA ZEB2-AS1 Augments Activity of Trophoblast Cells and Prevents the Development of Recurrent Spontaneous Abortion in Mice Through EZH2-Mediated CST3 Inhibition.

Recurrent spontaneous abortion (RSA) is the most common complication of pregnancy where reduced invasion of trophoblasts plays a major role. This work aimed to explore the effect of abnormally expressed long non-coding RNA (lncRNA) ZEB2-AS1 on the occurrence of RSA. Differentially expressed lncRNAs in trophoblast cells between healthy controls and patients with RSA were screened using the GEO database. Female CBA/J mice were allowed to mate with male DBA/2 mice to establish inbred mice with RSA. ZEB2-AS1 was poorly expressed in placental tissues and trophoblast cells in the condition of RSA. ZEB2-AS1 upregulation augmented proliferation, migration, and invasion of trophoblast cells in vitro. ZEB2-AS1 negatively regulated cystatin C (CST3) expression. Further overexpression of CST3 blocked the activity of trophoblast cells. ZEB2-AS1 recruited enhancer of EZH2 to the promoter region of CST3, which increased H3K27me3 modification to suppress CST3 expression. In vivo, overexpression of ZEB2-AS1 reduced embryo resorption rate and increased the weights of fetuses and placentas in mice with RSA. However, the protective roles of ZEB2-AS1 were blocked upon artificial silencing of EZH2 or upregulation of CST3. Taken together, this study demonstrates that ZEB2-AS1 enhances activity of trophoblast cells and prevents RSA development through reducing CST3 expression in an EZH2-dependent manner.

Triglyceride Induced Metabolic Inflammation: Potential Connection of Insulin Resistance and Recurrent Pregnancy Loss.

The underlying correlative mechanisms between Insulin resistance (IR) and recurrent pregnancy loss (RPL) in patients without polycystic ovarian syndrome (PCOS) remain inconclusive. To investigate the association between triglyceride (TG) levels, lymphocyte subsets, and IR in RPL patients without PCOS and obesity. Eighty-nine subjects with an unexplained RPL, independent of PCOS/obesity were enrolled in this study. A 75-g oral glucose tolerance test was performed on each subject with plasma tested for glucose and insulin. The fasting venous blood of all subjects was collected for routine clinical chemistry analysis. Lymphocyte subsets were analyzed by four-color flow cytometry. As a result, TG levels were significantly elevated in RPL patients with IR compared to those without IR. Pearson linear correlation model and receiver operating characteristic (ROC) curve analyses revealed a significant positive association between TG and HOMA-IR index value. In multiple logistic regression analysis, TG was significantly associated with the risk of hyperinsulinemia and increased CD3+CD4+/CD3+CD8+ ratio which was significantly negatively correlated with disposition index (DI30) and DI120, indicators for insulin sensitivity. In addition, DI30 and DI120 were significantly decreased in the higher CD3+CD4+/CD3+CD8+ group. Our findings showed that the elevated TG and altered immune responses in RPL patients with IR are independent of PCOS and obesity, and could be used as an indicator of IR in RPL patients. These results contribute to the understanding of the pathophysiology of IR in RPL for potential prevention and therapeutic targets.

Contrast Induced Nephropathy and 2-Year Outcomes of Iso-Osmolar Compared with Low-Osmolar Contrast Media after Elective Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: This study investigated the relative incidence of contrast induced nephropathy (CIN) and long-term outcomes between iso-osmolar contrast media (IOCM) and low-osmolar contrast media (LOCM) undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of 9,431 patients receiving elective PCI were enrolled in the cohort. The patients were divided into IOCM group and LOCM group. Propensity score matching (PSM) was applied to minimize the selection bias between groups. RESULTS: The multivariate analysis showed that the use of IOCM compared with LOCM did not affect the CIN incidence (odds ratio [OR], 0.912; 95% confidence interval [CI], 0.576-1.446; p=0.696). After PSM, the incidence of CIN was 1.5% and 4.0% in IOCM group (n=979) and LOCM group (n=979), respectively, p=0.001. IOCM significantly reduced the incidence of CIN compared with LOCM (OR, 0.393; 95% CI, 0.214-0.722; p=0.003). After 2 years of follow-up, the all-cause mortality was higher in IOCM group than LOCM group (2.1% vs. 0.9%, p<0.001). Cox regression analysis showed IOCM was not independent risk factor of 2-years all-cause mortality (OR, 0.849; 95% CI, 0.510-1.412; p=0.528). After PSM, the difference of all-cause death between groups disappeared (1.7% vs. 1.9%, p=0.739). Cox regression analysis showed that the use of IOCM compared with LOCM did not affect the incidence of 2-year all-cause mortality (OR, 1.037; 95% CI, 0.534-2.014; p=0.915). CONCLUSIONS: Compared with LOCM, IOCM significantly reduced the incidence of CIN after elective PCI, but had no significant effect on 2-year all-cause mortality.

Elevated percentage of CD3+T cells and pregnancy outcome in women with recurrent pregnancy loss.

BACKGROUND: Even though the immune factor is not yet established as a cause of recurrent pregnancy loss (RPL), tons of other studies have shown that a significant proportion of immune abnormalities exist in RPL. METHODS: We conducted a retrospective cohort study with 850 women who were diagnosed with RPL. The percentages of CD3+, CD3+CD4+ and CD3+CD8+T cells of each participant, detected by flow cytometry, were obtained before pregnancy and at 6 weeks of gestation as part of their routine medical examination. RESULTS: Peripheral blood CD3+ T cells prior to pregnancy (at baseline), increased significantly in women who had a miscarriage compared with the subsequent live birth group. Moreover, the percentage of CD3+ and CD3+CD4+T cells during pregnancy increased significantly as compared with the baseline level. After adjusting for potential confounders, the multiple regression equation showed that the CD3+ T cells <67.84% was associated with the risk of miscarriage (OR 1.05, 95% CI, 1.01 to 1.11, p = .04). Additionally, a nonlinear relationship was observed between the percentage of CD3+T cells and the risk of miscarriage. CONCLUSIONS: The risk of miscarriage increased as the percentage of population with CD3+ value below 67.84% has increased, nevertheless, the miscarriage risk did not increase further when the level of CD3+T cells was >67.84%.