characterization-functional-prediction-bacteria-ovarian

Characterization and Functional Prediction of Bacteria in Ovarian Tissues

The theory of a "sterile" female upper reproductive tract has been encountering increasing opposition due to advancements in bacterial detection. However, ...

First Affiliated Hospital of Xi’an Jiaotong University

Circulating tumor cells (CTCs) are an important part in the field of "liquid biopsy." However, major questions remain to be answered whether the mutations in the CTCs represent the mutations in primary tumor tissue and metastatic tumors. We compared the genetic mutations between CTCs and their matched tumors, and extracted data on the heterogeneity of the mutational status in CTCs and the change in mutations of CTCs before and during treatment. For mutations detected in single genes, we calculated the concordance of the mutations between the CTCs and primary tumor tissue. For mutations detected in multiple genes, we calculated the concordance of the mutations between the CTCs and primary/metastatic tumor tissue. The heterogeneity of the mutational status is clearly present in CTCs. For mutations detected in a single gene, the overall concordance of mutations is 53.05%. For mutations detected in multiple genes, the concordance of mutations is extremely different. The heterogeneity of the mutational status existed in single CTCs, and the mutational status of CTCs was discordant with that of tumor tissue.

The Discordance of Gene Mutations between Circulating Tumor Cells and Primary/Metastatic Tumor.

 If a woman suffers from congenital fibrinogen deficiency (CFD), she might undergo hypermenorrhea monthly and possibly to suffer from hemoperitoneum due to a ruptured follicle or corpus luteal cyst every month, which seriously threaten her health and quality of life. Here, we creatively used a combination of the levonorgestrel-releasing intrauterine system (LNG-IUS) and the combined oral contraceptives (COC) for a girl with CFD.  A 14-year-old girl presented with no obvious cause of persistent and severe lower abdominal pain that began 8 h prior. After examination, she was diagnosed as hemoperitoneum. CFD was diagnosed when she was 2 years old and she had two hospitalizations due to hemorrhagic anemia caused by menorrhagia. Therefore, after successful conservative treatment of hemoperitoneum, a combination of LNG-IUS and COC was used for the long-term conservative management of hypermenorrhea and hemoperitoneum. During the half-year of follow-up, she had hypomenorrhea without hemoperitoneum.  To the best of our knowledge, this was the first patient treated with such a procedure in the literature, and we recommend every woman with CFD at puberty or reproductive age receives this two-pronged treatment.

Two-Pronged Treatment of Hemoperitoneum and Abnormal Uterine Bleeding in an Adolescent Girl With Congenital Fibrinogen Deficiency.

 For women with intrauterine devices (IUDs), it is difficult to sample the endometrium when abnormal uterine bleeding occurs or when regular screening of endometrial cancer is proposed. The purpose of this study is to evaluate the validity of endometrial sampling using Li Brush in IUD users.  This study was a prospective cohort study and conducted in two parts. Part I was to assess the impact of Li Brush on the position of IUDs. Transvaginal ultrasound was used to locate IUDs before and after sampling. Part II was to explore the diagnostic accuracy of Li Brush in detecting endometrial lesions. IUD users with irregular uterine bleeding were recruited in the IUD group and IUD non-users who arranged for dilatation and curettage (D&C) were recruited in the control group. The endometrium was sampled by Li Brush for cells and by D&C for tissues in both groups. The satisfactoriness of sampling and validity of Li Brush were evaluated.  Seventeen cases in part I confirmed no significant difference in the position of IUDs before and after sampling ( = 0.20). 112 IUD users and 139 IUD non-users were recruited in part II. Li Brush achieved 94.64 and 92.09% satisfactory sampling rates in the IUD group and control group, respectively, without statistically significant difference between the two groups ( = 0.42). The Sensitivity and specificity of Li Brush for detection of endometrial lesions in IUD group were 95.35 and 87.76% respectively.  Li Brush used for endometrial biopsy did not affect the position of IUDs and had high yield of satisfactory samples and good validity for endometrial diagnoses. It was feasible to screen endometrial lesions by Li Brush for women with IUDs.

Clinical Evaluation of Li Brush Endometrial Samplers for Diagnosing Endometrial Lesions in Women With Intrauterine Devices.

To identify potential aberrantly differentially methylated genes (DMGs) correlated with chemotherapy response (CR) and establish a polygenic methylation prediction model of CR in epithelial ovarian cancer (EOC), we accessed 177 (47 chemo-sensitive and 130 chemo-resistant) samples corresponding to three DNA-methylation microarray datasets from the Gene Expression Omnibus and 306 (290 chemo-sensitive and 16 chemo-resistant) samples from The Cancer Genome Atlas (TCGA) database. DMGs associated with chemotherapy sensitivity and chemotherapy resistance were identified by several packages of R software. Pathway enrichment and protein-protein interaction (PPI) network analyses were constructed by Metascape software. The key genes containing mRNA expressions associated with methylation levels were validated from the expression dataset by the GEO2R platform. The determination of the prognostic significance of key genes was performed by the Kaplan-Meier plotter database. The key genes-based polygenic methylation prediction model was established by binary logistic regression. Among accessed 483 samples, 457 (182 hypermethylated and 275 hypomethylated) DMGs correlated with chemo resistance. Twenty-nine hub genes were identified and further validated. Three genes, anterior gradient 2 (AGR2), heat shock-related 70-kDa protein 2 (HSPA2), and acetyltransferase 2 (ACAT2), showed a significantly negative correlation between their methylation levels and mRNA expressions, which also corresponded to prognostic significance. A polygenic methylation prediction model (0.5253 cutoff value) was established and validated with 0.659 sensitivity and 0.911 specificity.

Article	Year
The Discordance of Gene Mutations between Circulating Tumor Cells and Primary/Metastatic Tumor. Molecular therapy oncolytics\| PubMed ID: 31650022	2019
Two-Pronged Treatment of Hemoperitoneum and Abnormal Uterine Bleeding in an Adolescent Girl With Congenital Fibrinogen Deficiency. Frontiers in medicine\| PubMed ID: 32509792	2020
Clinical Evaluation of Li Brush Endometrial Samplers for Diagnosing Endometrial Lesions in Women With Intrauterine Devices. Frontiers in medicine\| PubMed ID: 33330563	2020
A polygenic methylation prediction model associated with response to chemotherapy in epithelial ovarian cancer. Molecular therapy oncolytics\| PubMed ID: 33738340	2021

Dongxin Liang

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