Establishing a prognostic model with ferroptosis-related long non-coding RNAs in bladder cancer.

Background: Ferroptosis is a distinct form of cell death that has the potential to supersede the drug resistance that is commonly observed with current chemotherapeutic agents. As a result, ferroptosis presents a new and innovative therapeutic pathway for cancer treatment. The current understanding regarding the expression of genes associated with ferroptosis in bladder cancer (BLCA) and their prognostic implications remains unclear. Consequently, this study aimed to examine the potential prognostic value of ferroptosis-associated long non-coding RNAs (lncRNAs) in BLCA. Methods: The Cancer Genome Atlas (TCGA) was accessed to download RNA sequencing data and clinicopathological features of BLCA while accessing the FerrDb database to download ferroptosis-associated genes. The study calculated risk scores for ferroptosis-associated lncRNAs, and subsequently divided patients with BLCA into two groups, namely high- and low-risk, on the basis of the median risk score. Moreover, Kaplan-Meier (K-M) curves, Cox regression analysis, and column plots were utilized for evaluating the risk score prognostic value. Subsequently, the involvement of ferroptosis-associated mRNA, N6-methyladenosine (m6A) mRNA status, and immune responses was investigated for BLCA prognosis. Results: Thirty-six lncRNAs were identified to be differently expressed and linked to the prognosis of BLCA. The findings from the K-M curve analysis indicated a significant association between a high-risk lncRNA profile and poor BLCA prognosis. The area under curve (AUC) value of the receiver operating characteristic (ROC) curve was 0.810. The risk assessment model exhibited superior performance in predicting prognosis for BLCA compared to conventional clinicopathological features. Conclusions: Thirty-six lncRNAs were found to be linked to ferroptosis for the prognosis of patients with BLCA, and these results may provide new insights for treating BLCA.

Subsequent fertility after cesarean scar pregnancy: a retrospective analysis.

BACKGROUND: Cesarean scar pregnancy (CSP) refers to the implantation and growth of the gestational sac at a uterine scarring site due to a previous cesarean section. The effects of CSP on subsequent fertility have emerged as a clinical issue of importance in gynecology and obstetrics in China owing to the increasing rate of cesarean section over the past 30 years in combination with the abolition of the national family planning policy, allowing for subsequent pregnancies. Therefore, we aimed to investigate the effects of CSP treatment on subsequent fertility and pregnancy outcomes. METHODS: The study consecutively enrolled 499 women treated for CSP at Taizhou Hospital between January 2009 and December 2018. The study outcomes were the rate of secondary infertility and pregnancy outcomes. Clinical information was collected at the time of admission for CSP treatment. Information on subsequent fertility and pregnancy outcomes was collected via telephonic follow-up. RESULTS: Among the 499 women who met the inclusion criteria for CSP, 48 were lost to follow-up. Most women (74.9%, 338/451) did not express the desire for a subsequent pregnancy after CSP treatment. Among the 113 women who initially desired a subsequent pregnancy, 62 finally abandoned fertility plans. Among the 51 women who pursued pregnancy, 48 pregnancies were recorded in 43 women, infertility secondary to CSP treatment was identified in 15.7% (8/51) of women, and 60.8% (31/51) of women achieved full-term pregnancy, with placenta accreta spectrum identified in two women, one requiring a hysterectomy during cesarean section due to massive bleeding. Among the 16 women treated with uterine artery embolization combined with uterine aspiration and 18 women treated by ultrasound-guided local lauromacrogol injection combined with uterine aspiration, a successful full-term pregnancy rate of 68.8% (11/16) and 88.9% (16/18), respectively, was achieved. There were five cases of recurrent CSP among all 76 pregnancies (6.6%). CONCLUSION: Over a long-term follow-up of women after CSP treatment, a high successful fertility rate was identified, with also an increased CSP recurrence rate. Uterine artery embolization combined with uterine aspiration and ultrasound-guided local lauromacrogol injection combined with uterine aspiration showed high rates of successful post-treatment fertility and pregnancy.

Coronatine-Based Gene Expression Changes Impart Partial Resistance to Fall Armyworm (Spodoptera frugiperda) in Seedling Maize.

In recent years, Spodoptera frugiperda (S. frugiperda, Smith) has invaded China, seriously threatening maize production. To explore an effective method to curb the further expansion of the harm of the S. frugiperda, this experiment used maize seedlings of the Zhengdan 958 three-leaf stage (V3) of maize as the material to study the effect of coronatine (COR) on the ability of maize to resist insects (S. frugiperda) at the seedling stage. The results showed that when maize was sprayed with 0.05 µM COR, the newly incubated larvae of S. frugiperda had the least leaf feeding. It was found that 0.05 µM COR significantly increased the contents of abscisic acid (ABA) and jasmonate (JA) in maize leaves through the determination of hormone content. Moreover, transcriptome sequencing revealed that the expression of six genes (ZmBX1, ZmBX2, ZmBX3, ZmBX4, ZmBX5 and ZmBX6), which are associated with the synthesis of benzoxazinoid, were upregulated. Nine genes (ZmZIM3, ZmZIM4, ZmZIM10, ZmZIM13, ZmZIM18, ZmZIM23, ZmZIM27, ZmZIM28 and ZmZIM38) of JA-Zim Domain (JAZ) protein in the JA signal pathway, and seven genes (ZmPRH19, ZmPRH18, Zm00001d024732, Zm00001d034109, Zm00001d026269, Zm00001d028574 and Zm00001d013220) of ABA downstream response protein Group A Type 2C Protein Phosphatase (PP2C) were downregulated. These results demonstrated that COR could induce anti-insect factors and significantly improve insect resistance in seedling maize, which laid a theoretical foundation for further study of the mechanism of COR improving insect resistance in seedling maize, and provided data references for the use of COR as an environmentally friendly pest control method.

A systemic review of T-cell epitopes defined from the proteome of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remains in a global pandemic, and no eradicative therapy is currently available. Host T cells have been shown to play a crucial role in the antiviral immune protection and pathology in Coronavirus disease 2019 (COVID-19) patients; thus, identifying sufficient T-cell epitopes from the SARS-CoV-2 proteome can contribute greatly to the development of T-cell epitope vaccines and the precise evaluation of host SARS-CoV-2-specific cellular immunity. This review presents a comprehensive map of T-cell epitopes functionally validated from SARS-CoV-2 antigens, the human leukocyte antigen (HLA) supertypes to present these epitopes, and the strategies to screen and identify T-cell epitopes. To the best of our knowledge, a total of 1349 CD8+ T-cell epitopes and 790 CD4+ T-cell epitopes have been defined by functional experiments thus far, but most are presented by approximately twenty common HLA supertypes, such as HLA-A0201, A2402, B0702, DR15, DR7 and DR11 molecules, and 74-80% of the T-cell epitopes are derived from S protein and nonstructural protein. These data provide useful insight into the development of vaccines and specific T-cell detection systems. However, the currently defined T-cell epitope repertoire cannot cover the HLA polymorphism of major populations in an indicated geographic region. More research is needed to depict an overall landscape of T-cell epitopes, which covers the overall SARS-CoV-2 proteome and global patients.

Catalyst-Free Accelerated Three-Component Synthesis of Betti Bases in Microdroplets.

Due to their important roles in medicine and asymmetric metal catalysis, the formation of Betti bases has attracted wide interest in organic chemical community. Traditional multicomponent reaction methods for synthesizing Betti bases normally require long reaction times under harsh conditions (high temperature, microwave or ultrasonic irradiation, etc.) in the presence of various catalysts. In this study, we developed a mild, highly efficient and environmentally friendly method to synthesize Betti bases without the use of any catalysts in microdroplets. The Betti reaction was accelerated by 6.53×103 in microdroplets by comparing the measured rate constant in bulk. Fifteen Betti bases were synthesized by the microdroplet method using a variety of aldehydes, naphthols and amines with 68-98 % yields at a scaled-up amount of 1.9 g h-1 . Overall it is an attractive alternative to classic organic synthesis for the construction of Betti bases and derivatives.

Artificial Intelligence Based Study Association between p53 Gene Polymorphism and Endometriosis: A Systematic Review and Meta-analysis.

Background: The P53 gene is critical to the onset and progression of cancers. Currently, relevant study findings indicate that the p53 gene may have a strong association with the risk of endometriosis, but these findings have not been united. To gather more statistically meaningful clinical data, we used meta-analysis to examine the relationship between the rs1042522 single nucleotide polymorphism of the tumor suppressor gene p53 and the incidence of endometriosis. Methods: Through a comprehensive literature survey of PubMed, MEDLINE, EMBASE, Springer, and Web of Science literature databases, we obtained a clinical control case study on the relationship between p53 gene polymorphism and the prevalence of female endometriosis and finally traced the relevant references included. The quality of the literature included in this study was evaluated, and Revman5.3 was used to complete the meta-analysis. Results: This research includes eight publications. The total number of cases in the study group was 1551, whereas the total number of cases in the control group was 1440. The findings of the sensitivity analyses of each omitted piece of the literature revealed no significant difference. The results of the meta-analysis showed that there were significant differences in the GG gene frequency (OR = 0.56, 95%CI (0.38, 0.92), P = 0.003), allele G (OR = 2.46, 95%CI (1.41,4.29), P = 0.002), and allele C (OR = 0.62, 95%CI (0.46, 0.84), P = 0.002) between the study group and the control group (P < 0.01), but there was no significant difference in the GC gene frequency (OR = 1.17, 95%CI (1.01,1.36), P = 0.03), and the CC gene frequency (OR = 1.25, 95%CI (0.85,1.82), P = 0.26) (P > 0.01). Conclusion: Our study results show that there is a significant correlation between the single nucleotide of the p53 gene and the incidence rate of female endometriosis, in which the decrease of the GG gene frequency and the increase of allele C are likely to increase the risk of such diseases.

Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8+ T Cell Response in HLA-A Transgenic Mice.

Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response. Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ+/CD8+ T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.

Screening and Identification of HBV Epitopes Restricted by Multiple Prevalent HLA-A Allotypes.

Although host T cell immune responses to hepatitis B virus (HBV) have been demonstrated to have important influences on the outcome of HBV infection, the development of T cell epitope-based vaccine and T cell therapy and the clinical evaluation of specific T cell function are currently hampered markedly by the lack of validated HBV T cell epitopes covering broad patients. This study aimed to screen T cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and presenting by thirteen prevalent human leukocyte antigen (HLA)-A allotypes which gather a total gene frequency of around 95% in China and Northeast Asia populations. 187 epitopes were in silico predicted. Of which, 62 epitopes were then functionally validated as real-world HBV T cell epitopes by ex vivo IFN-γ ELISPOT assay and in vitro co-cultures using peripheral blood mononuclear cells (PBMCs) from HBV infected patients. Furthermore, the HLA-A cross-restrictions of each epitope were identified by peptide competitive binding assay using transfected HMy2.CIR cell lines, and by HLA-A/peptide docking as well as molecular dynamic simulation. Finally, a peptide library containing 105 validated epitopes which cross-binding by 13 prevalent HLA-A allotypes were used in ELISPOT assay to enumerate HBV-specific T cells for 116 patients with HBV infection. The spot forming units (SFUs) was significantly correlated with serum HBsAg level as confirmed by multivariate linear regression analysis. This study functionally validated 62 T cell epitopes from HBV main proteins and elucidated their HLA-A restrictions and provided an alternative ELISPOT assay using validated epitope peptides rather than conventional overlapping peptides for the clinical evaluation of HBV-specific T cell responses.

Effect of Mirena placement on reproductive hormone levels at different time intervals after artificial abortion.

BACKGROUND: Improper methods of contraception greatly increase the risk of abortion, cervical or endometrial lesions, and the number of recurrent artificial abortions. These complications result in the deterioration of a patient's outcome. Further, the proportion of artificial abortions is highest among unmarried females. Placement of an intrauterine device, such as the Mirena, after an artificial abortion may decrease the likelihood of an endometrial injury caused by recurrent abortions while significantly improving its contraceptive effects. AIM: To discuss the effect of Mirena placement on reproductive hormone levels at different time points after an artificial abortion. METHODS: Women (n = 119) undergoing an artificial abortion operation were divided into the study (n = 56) and control (n = 63) groups. In the study group, the Mirena was inserted immediately after the artificial abortion, whereas in the control group, it was inserted 4-7 d after the onset of the first menstrual cycle after abortion. All participants were followed-up for 6 mo to observe the continuation and expulsion rates and adverse reactions and to measure the levels of serum estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS: The continuation rates were 94.64% and 93.65% in the study group and the control group, respectively. The expulsion rates were 1.79% and 3.17% in the study group and the control group, respectively. There was no statistically significant difference between the two groups (P > 0.05). There were also no statistically significant differences in the proportion of patients with bacterial vaginitis, trichomonas vaginitis, or cervicitis between the groups (P > 0.05). Six months after Mirena placement, E2 Levels were 45.50 ± 7.13 pg/mL and 42.91 ± 8.10 pg/mL, FSH 13.60 ± 3.24 mIU/mL and 14.54 ± 3.11 mIU/mL, and LH 15.11 ± 2.08 mIU/mL and 14.60 ± 3.55 mIU/mL in the study and control groups, respectively. There were no significant differences in hormone levels between the two groups (P > 0.05). There were also no statistically significant differences in the proportions of abnormal menstruation, prolonged menstruation, or pain during intercourse between the study and control groups after Mirena placement (P > 0.05). There were no statistically significant differences in uterine volume, sexual desire, sexual activity, or the sexual satisfaction score between the study and control groups before and after Mirena placement (P > 0.05). CONCLUSION: Placement of a Mirena intrauterine device immediately after an artificial abortion does not increase the risk of adverse reactions and can help prevent endometrial injury caused by recurrent abortions.

Identification of HLA-A2 restricted epitopes of glypican-3 and induction of CTL responses in HLA-A2 transgenic mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality, but lacks effective treatments. Carcinoembryonic antigen glypican-3 (GPC3) is a tumor-associated antigen overexpressed in HCC but rarely expressed in healthy individuals and thus is one of the most promising therapeutic targets. T cell epitope-based vaccines may bring light to HCC patients, especially to the patients at a late stage. However, few epitopes from GPC3 were identified to date, which limited the application of GPC3-derived epitopes in immunotherapy and T cell function detection. In this study, a total of 25 HLA-A0201 restricted GPC3 epitopes were in silico predicted and selected as candidate epitopes. Then, HLA-A0201+/GPC3+ HCC patients' PBMCs were collected and co-stimulated with the candidate epitope peptides in ex vivo IFN-γ Elispot assay, by which five epitopes were identified as real-world epitopes. Their capacity to elicit specific CD8+ T cells activation and proliferation was further confirmed by in vitro co-cultures of patients' PBMCs with peptide, in vitro co-cultures of healthy donors' PBLs with DCs and peptide, T2 cell binding assay as well as HLA-A2 molecule stability assay. Moreover, the in vivo immunogenicity of the five validated epitopes was confirmed by peptides cocktail/poly(I:C) vaccination in HLA-A0201/DR1 transgenic mice. Robust epitope-specific CD8+ T cell responses and cytotoxicity targeting HepG2 cells were observed as detected by IFN-γ Elispot, intracellular IFN-γ staining and cytolysis assay. This study provided novel GPC3 CTL epitopes for the development of T cell epitope vaccines and evaluation of GPC3 specific T cell responses.

Clinical Application of Noninvasive Prenatal Testing for Pregnant Women with Assisted Reproductive Pregnancy.

OBJECTIVE: This paper analyzes the clinical significance of noninvasive prenatal testing (NIPT) for fetal chromosome aneuploidy in the screening of in vitro fertilization-embryo transfer (IVF) pregnancies. METHODS: The study subjects consisted of 3163 IVF-pregnant women who underwent NIPT at the Women's Hospital, School of Medicine, Zhejiang University and Taizhou Hospital, Zhejiang Province from February 2015 to June 2019. Fetal or neonatal karyotype analysis was carried out in high-risk patients, with subsequent follow-up on pregnancy outcomes. RESULTS: NIPT results of 3163 pregnant women suggested 20 cases of high-risk fetal chromosome aneuploidy, of which 2185 cases were a single pregnancy. Of the 13 cases of high-risk chromosome aneuploidy in single pregnancies, seven were true positive, and six were false positive according to fetal or newborn chromosomal karyotype diagnosis. Twin pregnancies accounted for 978 cases in which NIPT indicated seven cases of high-risk chromosome aneuploidy; six of these cases were true positive, and one case was false positive according to fetal or newborn chromosomal karyotype diagnosis. The specificity, positive predictive value, and false-positive rate of trisomy 21 syndrome in IVF single embryo NIPT were 99.86%, 62.5%, and 0.14%, respectively. The specificity, positive predictive value, and false-positive rate of trisomy 18 syndrome were 99.95%, 66.67%, and 0.05%, respectively. The specificity of trisomy 13 syndrome was 99.91%, and the false-positive rate was 0.09%. The specificity of trisomy 21 syndrome in IVF twin NIPT was 99.89%, the positive predictive value was 83.33%, and the false-positive rate was 0.11%. The specificity and positive predictive value of fetal trisomy 18 syndrome were 100.00%, and the false-positive rate of it were 0.00%. Sensitivity and false-negative rates were 100% in all cases. CONCLUSION: NIPT is an ideal prenatal test for IVF-pregnant women due to its high sensitivity and specificity in screening for fetal aneuploidy.

Receptor-Binding Domain Proteins of SARS-CoV-2 Variants Elicited Robust Antibody Responses Cross-Reacting with Wild-Type and Mutant Viruses in Mice.

Multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have spread around the world, but the neutralizing effects of antibodies induced by the existing vaccines have declined, which highlights the importance of developing vaccines against mutant virus strains. In this study, nine receptor-binding domain (RBD) proteins of the SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1 lineages) were constructed and fused with the Fc fragment of human IgG (RBD-Fc). These RBD-Fc proteins contained single or multiple amino acid substitutions at prevalent mutation points of spike protein, which enabled them to bind strongly to the polyclonal antibodies specific for wild-type RBD and to the recombinant human ACE2 protein. In the BALB/c, mice were immunized with the wild-type RBD-Fc protein first and boosted twice with the indicated mutant RBD-Fc proteins later. All mutant RBD-Fc proteins elicited high-level IgG antibodies and cross-neutralizing antibodies. The RBD-Fc proteins with multiple substitutions tended to induce higher antibody titers and neutralizing-antibody titers than the single-mutant RBD-Fc proteins. Meanwhile, both wild-type RBD-Fc protein and mutant RBD-Fc proteins induced significantly decreased neutralization capacity to the pseudovirus of B.1.351 and P.1 lineages than to the wild-type one. These data will facilitate the design and development of RBD-based subunit vaccines against SARS-COV-2 and its variants.

Screening HLA-A-restricted T cell epitopes of SARS-CoV-2 and the induction of CD8+ T cell responses in HLA-A transgenic mice.

Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019 (COVID-19), this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses. A total of 120 CD8+ T cell epitopes from the E, M, N, S, and RdRp proteins were functionally validated. Among these, 110, 15, 6, 14, and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; in addition, four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants. Then, 31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or poly (lactic-co-glycolic acid) nanoparticles, and these vaccines elicited robust and specific CD8+ T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice. In contrast to previous research, this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes, provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations, and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype, which initially confirmed the in vivo feasibility of 9- or 10-mer peptide cocktail vaccines against SARS-CoV-2. These data will facilitate the design and development of vaccines that induce antiviral CD8+ T cell responses in COVID-19 patients.

Design and Fabrication of the Evolved Zeolitic Imidazolate Framework-Modified Polylactic Acid Nonwoven Fabric for Efficient Oil/Water Separation.

Design of durable and recyclable superhydrophobic materials for oil/water separation is a major concern in the field of wastewater treatment. Functionalization of a biodegradable matrix with controllable grown crystals brings out a new research perspective. In this study, multiscale zeolitic imidazolate frameworks (ZIFs) were grown and decorated on a polylactic acid (PLA) nonwoven fabric (NWF) to construct a superhydrophobic material by an in situ growth method and a spraying process. The stable superhydrophobic layer contains two kinds of ZIF crystals showing microscale flake-like structures and nanoscale particles. The morphology and surface energy of such a hierarchically structured ZIF-modified PLANWF is controllable by the adjustment of experimental parameters. The as-prepared PLA hybrid materials exhibit high separation efficiency and recyclability as for water-nitromethane and water-toluene mixtures. Based on the wetting envelopes of the ZIF-modified PLA material, its separation performance for various oil/water mixtures can be preliminarily assessed before the application.

Galectin-1 expression in the serum and placenta of pregnant women with fetal growth restriction and its significance.

BACKGROUND: This study aims to investigate galectin-1 (Gal-1) expression in the serum and placenta of pregnant women with fetal growth restriction (FGR) and its significance. METHODS: Thirty-one pregnant women with single-birth FGR but without comorbidities, eight pregnant women with FGR and preeclampsia (PE), and eight pregnant women with FGR and gestational diabetes mellitus (GDM) were enrolled as the study group, while 20 pregnant women with normal singleton pregnancy in the same period were enrolled as the control group. The serum Gal-1 level was detected using an enzyme-linked immunosorbent assay (ELISA), and Gal-1 expression in the placenta was detected by western blot. RESULTS: The results revealed that, compared with the control group, the serum Gal-1 level decreased in the women with FGR without comorbidities, and the difference was statistically significant (P < 0.001). Compared with the control group, the difference in serum Gal-1 expression in the FGR-PE group was not statistically significant (P = 0.29). The peripheral serum Gal-1 level decreased in the FGR-GDM group compared with the control group, and the difference was statistically significant (P < 0.001). The serum Gal-1 level was positively correlated with birth weight (r2 = 0.172, P < 0.01). Compared with the control group, the Gal-1 expression level decreased in the placenta of the pregnant women with FGR without comorbidities (P < 0.05). CONCLUSIONS: Gal-1 exhibits low expression in the serum and placenta of pregnant women with FGR. In addition, Gal-1 may be involved in the pathogenesis of FGR and could represent a new diagnostic marker of the disease.

Efficiency of non-invasive prenatal screening in pregnant women at advanced maternal age.

BACKGROUND: Non-invasive prenatal screening (NIPS) is widely used as the alternative choice for pregnant women at high-risk of fetal aneuploidy. However, whether NIPS has a good detective efficiency for pregnant women at advanced maternal age (AMA) has not been fully studied especially in Chinese women. METHODS: Twenty-nine thousand three hundred forty-three pregnant women at AMA with singleton pregnancy who received NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), receiver operating characteristic (ROC) curves and the Youden Index for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed. RESULTS: The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11, 99.96, 90.98, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100, 99.94, 67.92, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100, 99.96, 27.78, and 100%, respectively. The prevalence of fetal trisomy 21 increased exponentially with maternal age. The high-risk percentage incidence rate of fetal trisomy 21 was significantly higher in the pregnant women at 37 years old or above than that in pregnant women at 35 to 37 years old. (Youden index = 37). CONCLUSION: It is indicated that NIPS is an effective prenatal screening method for pregnant women at AMA.

Umbilical cord plasma-derived exosomes from preeclamptic women induce vascular dysfunction by targeting HMGCS1 in endothelial cells.

Hypertension is one of the major clinical manifestations of preeclampsia. Vascular dysfunction is crucial for the occurrence and progression of hypertension. Exosomes are emerging as mediators of intercellular communication and can participate in angiogenesis. In this study, we hypothesize that umbilical cord plasma-derived exosomes from preeclamptic women (PE-uexo) impair vascular development by regulating endothelial cells. Here, umbilical cord plasma samples from women with normal pregnancies and matched preeclamptic patients were used to isolate circulating exosomes. Proliferation, Transwell and tube formation assays indicated that PE-uexo impaired the angiogenesis of human umbilical vein endothelial cells (HUVECs). On the basis of microarray analysis of HUVECs treated with PE-uexo or exosomes from women with normal pregnancies, we showed that the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) was decreased in the PE-uexo-treated HUVECs. Furthermore, downregulation of HMGCS1 in HUVECs attenuated the proliferation and migration of these cells. Interestingly, HMGCS1 was decreased in P0 HUVECs from preeclamptic pregnancies compared with normotensive pregnancies. Together, these observations suggest that PE-uexo disrupts normal function in vascular endothelial cells by targeting HMGCS1, which may result in vascular disorders in the offspring.

Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China.

OBJECTIVE: Prolylcarboxypeptidase (PRCP) is both involved in the Kallikrein-Kinin system (KKS) and renin-angiotensin-aldosterone system (RAAS). This study aimed to determine the genetic impact of PRCP gene polymorphisms on essential hypertension (EH) in an isolated population from a remote region of China. METHODS: A haplotype-based study was investigated in 346 EH patients and 346 normal subjects and all samples were Hani minority residents in Southwest China. A total of 11 tag single nucleotide polymorphisms (SNPs) in PRCP gene were tested by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Single site analysis found that PRCP gene 3'UTR SNP rs3750931 was associated with EH. The minor allele G of rs3750931 was more prevalent in the EH patients compared to control subjects after Bonferroni correction (p < 0.05). Moreover, the rs3750931 G allele carriers showed higher average blood pressure (BP) level among the subjects. The H2 (GAGCACTAACA) haplotype without rs3750931 G allele showed the protective effect for EH (OR = 0.68, 95 CI 0.54-0.85, p = 0.001). CONCLUSION: The present study indicated PRCP gene rs3750931 was associated with the risk of EH. This SNP G allele could be considered as one of risk markers for EH in Hani population.

Continuous renal replacement therapy rescues severe haemorrhagic fever with renal syndrome in pregnancy: a case report.

BACKGROUND: Haemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease caused by various types of viruses of the genus Hantavirus, which are mainly transmitted by contact with the infected rodents and their droppings. Pregnancy complicated with HFRS is rare; however, adverse maternal and foetal outcomes may be noted. In this report, we describe a case involving a pregnant woman with HFRS who was in a state of multiple organ dysfunction syndrome (MODS) and was successfully treated with continuous renal replacement therapy (CRRT). CASE PRESENTATION: A 32-year-old pregnant woman at 29 weeks of gestation was hospitalised for a fever and upper respiratory tract infection due to HFRS in winter. Persistent fever, coagulation disorder, thrombocytopenia, electrolyte imbalance, abnormal liver function, and renal failure were noted during the progression of the disease. The patient was treated with CRRT. She recovered after 21 days, and delivered a live infant by caesarean section at 38 weeks of gestation. Furthermore, obvious abnormalities were not detected during the follow-up of the mother and infant at 42 days, 3 months, 6 months, and 1 year after the delivery. CONCLUSIONS: Early diagnosis, timely application of CRRT, and comprehensive treatment may be essential for the successful treatment of patients with HFRS during pregnancy.

[Genetic analysis of a mosaic case with low proportion mutation of TSC2 gene].

OBJECTIVE: To perform gene mutation analysis in a patient with atypical clinical manifestations of tuberous sclerosis (TSC) for definite diagnosis. METHODS: Peripheral blood DNA was obtained from a patient with clinically suspected TSC and her parents, and all exons and their flanking sequences of TSC1 and TSC2 genes in the proband were sequenced by whole exome sequencing to determine the candidate pathogenic mutations. At the same time, Sanger sequencing was performed to verify the peripheral blood DNA of the patient and her parents. And the mosaic percentage of the mutation in the proband's somatic cells was detected by the droplet digital PCR method. RESULTS: A heterozygous nonsense mutation c.1096G>T (p.E366*) was identified in the exon 11 of the TSC2 gene, which only had a small mutation peak. A lower percentage of the mutation was found in the DNA of the patient than that in the public database, therefore the possibility of mosaicism might not be excluded. In addition, the droplet digital PCR method demonstrated that the proband was a c.1096G>T mutant mosaicism, and the mosaic percentage was 14%. CONCLUSIONS: The somatic mosaic mutation c.1096G>T (p.e366*) may be responsible for the phenotype of TSC in this patient. And the drop digital PCR is expected to be a diagnostic method for somatic cells mosaicism.