Case report of thrombotic thrombocytopenic purpura during pregnancy with a review of the relevant research.

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case. PATIENT CONCERNS: A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days. DIAGNOSES: TTP. INTERVENTIONS: At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective. OUTCOMES: The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged. LESSONS SUBSECTIONS: The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.

Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion/Microduplication Syndromes.

OBJECTIVE: We aimed to evaluate the clinical performance of expanded noninvasive prenatal testing (NIPT-Plus) for the detection of aneuploidies and microdeletion/microduplication syndromes. METHODS: A total of 7177 pregnant women were enrolled in the study from June 2020 to March 2022 at Xijing Hospital, China. Cases with NIPT-Plus-positive results were further confirmed by chromosomal karyotyping and a chromosomal microarray analysis. RESULTS: A total of 112 positive cases (1.56%) were identified by NIPT-Plus, including 60 chromosome aneuploidies and 52 microdeletion/microduplication syndromes. Ninety-five cases were validated by amniocentesis, and 57 were confirmed with true-positive results, comprising 18 trisomy 21, 4 trisomy 18, 1 trisomy 13, 17 sex chromosome aneuploidies, 1 other aneuploidy, and 16 microdeletion/microduplication syndromes. The positive predictive value of total chromosomal abnormalities was 60% (57/95). For trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, other aneuploidies and microdeletion/microduplication syndromes, the sensitivity was all 100%, the specificity was 100, 99.986, 100, 99.888, 99.958, and 99.636%, and the positive predictive value was 100, 80, 100, 68, 25, and 38.10%, respectively. For all clinical characteristics, the abnormal maternal serum screening group was found to have the highest prevalence of chromosomal abnormalities (1.54%), and the ultrasound abnormality group presented the highest positive predictive value (73.33%). CONCLUSIONS: NIPT-Plus has great potential for the detection of aneuploidies and microdeletion/microduplication syndromes owing to its high sensitivity, safety, and specificity, which greatly reduces unnecessary invasive procedures and the risk of miscarriage and allows informed maternal choice.

Maternal Outcomes Among Pregnant Women With Congenital Heart Disease-Associated Pulmonary Hypertension.

BACKGROUND: Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. METHODS: Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. RESULTS: A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. CONCLUSIONS: Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

BACs-on-Beads Assay for the Prenatal Diagnosis of Microdeletion and Microduplication Syndromes.

OBJECTIVE: To evaluate the clinical value of BACs-on-Beads (BoBs) assay in detection of microdeletion and microduplication syndromes. METHODS: A total of 6,814 cases of amniotic fluid cells collected from January 2015 to July 2020 in our hospital were analyzed by chromosomal karyotyping and BoBs assay. Fluorescence in situ hybridization (FISH) or chromosomal microarray analysis (CMA) provided further validation for the cases of microdeletion and microduplication. RESULTS: Thirty microdeletion and microduplication syndromes were identified by BoBs with an incidence of ~1/227, including 22q11.2 microduplication (0.044%, 3/6814), DiGeorge I syndrome (0.044%, 3/6814), 17p11.2 microduplication (0.015%, 1/6814), Smith-Magenis syndrome (0.015%, 1/6814), 17p11.2p11.3 microduplication (0.015%, 1/6814), Williams-Beuren syndrome (0.088%, 6/6814), 7q11.2 microduplication (0.029%, 2/6814), DiGeorge II syndrome (0.015%, 1/6814), 18p11.32p11.21 microduplication (0.015%, 1/6814), Wolf-Hirschhorn syndrome (0.029%, 2/6814), 4p16.3 microduplication (0.015%, 1/6814), Langer-Giedion syndrome (0.015%, 1/6814), Miller-Dieker syndrome (0.015%, 1/6814), Cri du Chat syndrome (0.015%, 1/6814), Xp22.31 microdeletion (0.059%, 4/6814), Prader-Willi syndrome (0.015%, 1/6814). High concordance was obtained between BoBs and FISH or CMA. However, only four cases were detected by chromosomal karyotyping. CONCLUSION: BoBs assay can rapidly detect microdeletion and microduplication syndromes, which compensates the shortcomings of conventional chromosomal karyotyping and greatly improves the efficiency and accuracy of prenatal diagnosis.

CXCL5 contributes to the tumorigenicity of cervical cancer and is post-transcriptionally regulated by miR-577.

BACKGROUND: C-X-C motif chemokine ligand 5 (CXCL5), an important chemokine, has been validated to promote human tumorigenesis. However, the clinical significance and the underlying molecular mechanisms of CXCL5 have not been completely explored in cervical cancer. Herein, the aim was to investigate miR-577-mediated CXCL5 signaling in cervical tumorigenicity. MATERIAL AND METHODS: Sixty-one pairs of cervical cancer specimens and para-carcinoma tissues were collected to measure miR-577 and CXCL5 expression levels. miR-577 mimics and/or si-CXCL5 were transfected into cervical cancer cell lines, Hela, and SiHa cells, to determine their effect on cell proliferation, migration and apoptosis. RESULTS: Our results demonstrated that CXCL5 is overexpressed in cervical cancer tissues and cell lines. Knockdown of CXCL5 with specific siRNA transfection in Hela and SiHa cells significantly inhibited cell proliferation and migration and induced apoptosis in vitro. We also report that CXCL5 is a direct target of miR-577. Additionally, transfection of miR-577 mimics can inhibit CXCL5 protein expression, but not mRNA in Hela cells. miR-577 mimic transfection significantly inhibits migration and induces apoptosis in Hela and SiHa cells. However, the antineoplastic activities of miR-577 are reversed by overexpression of CXCL5 in vitro. CONCLUSIONS: Overexpression of CXCL5 is involved in tumor development of cervical cancer. Inhibition of CXCL5 by its post-transcriptional regulator, miR-577, may provide a promising therapeutic strategy for patients with cervical cancer.

Neurofibromin 1 expression is negatively correlated with malignancy and prognosis of epithelial ovarian cancer.

Epithelial ovarian cancer ranks as the 5th most deadly female cancer. However, few effective biomarkers have been identified for clinical application. Thus, it is critical to identify differentially expressed genes in epithelial ovarian cancer patient samples. Our work has focused on a tumor suppressor gene Neurofibromin 1 and its role in epithelial ovarian cancer pathology. We examined 124 samples of benign ovarian tissues, borderline ovarian tissues, and epithelial ovarian cancer tissues for NF1 expression by immunohistochemistry and further validated our results using RT-PCR and Western blot. We next analyzed the follow-up information with pathological features using Kaplan-Meier univariate survival analysis and Cox regression multivariate analysis. First, our results show that the mRNA level and protein level of NF1 are significantly decreased in epithelial ovarian cancer patients. Second, NF1 expression is negatively associated with 5-year overall survival, lymph node metastasis, and tumor size. Furthermore, our data also suggests that NF1 expression is a protective factor for epithelial ovarian cancer prognosis. NF1 is negatively regulated in EOC patients and low expression of NF1 is associated with lymph node metastasis. More importantly, patients that have lost NF1 showed poorer prognosis and five-year overall survival.

Deregulation of WNT2/FZD3/ß-catenin pathway compromises the estrogen synthesis in cumulus cells from patients with polycystic ovary syndrome.

Mechanistic insight into estrogen deficiency by polycystic ovary syndrome (PCOS) remains a longstanding challenge in reproductive medicine. Recent advance suggest that Wingless-type MMTV integration site family members (WNTs), in concert with its Frizzled (FZD) receptors, regulate normal folliculogenesis, luteogenesis and ovarian steroidogenesis. However, no studies have so far investigated any causality between WNT-FZDs interactions and disrupted estrogen synthesis under certain pathological conditions. Here, we show that (i) FZD3 expression was significantly up-regulated in the cumulus cells (CCs) from PCOS patients. This up-regulation, along with the activation of WNT2/ß-Catenin pathway, was tightly associated with insulin resistance and estrogen deficiency, two hallmarks of PCOS. (ii) Overexpression of exogenous FZD3 in human granulosa cell COV434 impaired long-term FSH incubation-induced CYP19A1 transactivation and the recruitment of ß-Catenin onto CYP19A1 promoter, and subsequently compromised FSH-stimulated estrogen production. (iii) Conversely, inhibition of FZD3 expression exhibited a therapeutic effect on estrogen synthesis in PCOS CCs. Thus, excessive FZD3 expression in CCs may act as a brake on steroidogenic activation that is normally overcome by FSH stimulation. Future endeavor in this field should help to elucidate the complicated crosstalk between energy metabolism and endocrine cells through WNT/FZD signaling molecules.