1.Changes in myeloid-derived suppressor cells (MDSC), Treg and Th17 cells in peripheral blood of patients with cervical human papillomavirus (HPV) infection
Chinese Journal of Microbiology and Immunology 2017;37(8):586-593
Objective To investigate the changes in myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg) and T helper 17 (Th17) cells in peripheral blood of patients with HPV infection and cervical diseases including ectopic cervical columnar epithelium (CE), cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CC), and to analyze the roles of MDSC, Treg and Th17 cells in the development of cervical diseases.Methods This study enrolled 120 HPV-positive patients with cervical diseases (18 cases of CE, 50 cases of CIN, 52 cases of CC), 20 HPV-negative patients with cervical diseases (10 cases of CE and 10 cases of CIN) and 20 healthy subjects from March 2011 to December 2016.Changes in MDSC, Treg and Th17 cells in peripheral blood of all patients were detected by flow cytometry.Results Percentages of MDSC, Treg and Th17 cells in peripheral blood of patients who were positive for HPV were significantly higher than those in HPV-negative patients (P<0.05).Besides, percentages of these cells gradually increased with the exacerbation of cervical disease (CE-CINⅠ-CINⅡ-CINⅢ-CC) (P<0.05).Patients who were infected with high-risk HPV had significantly higher percentages of MDSC, Treg and Th17 cells in peripheral blood than those infected with low-risk HPV (P<0.05).Changes of MDSC, Treg and Th17 cells in peripheral blood of HPV-positive patients with cervical cancer were related to International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation, lymph node metastasis and vascular invasion (P<0.05).MDSC, Treg and Th17 cells in peripheral blood of all patients were significantly reduced after treatment (P<0.05).Patients whose status changed from HPV-positive to HPV-negative following treatment also showed significantly decreased MDSC, Treg and Th17 cells in peripheral blood as compared with those who remained HPV-positive (P<0.05).MDSC, Treg and Th17 cells in peripheral blood of HPV-positive patients with cervical diseases were positively correlated (r=0.599, 0.677, 0.648;P<0.05).Conclusion MDSC, Treg and Th17 cells in peripheral blood of patients with HPV infection are associated with the pathological process, severity and clinical pathological features of cervical diseases as well as therapeutic effects.Therefore, they can be used as biomarkers to detect the occurrence and development of HPV-positive cervical diseases.
2.Desmoid fibromatosis of the breast:clinicopathological analysis of twenty-six cases and review of literatures
Huifen HUANG ; Pan LI ; Huayan REN ; Yuqiong LIU ; Wencai LI ; Huixiang LI
Chinese Journal of Clinical and Experimental Pathology 2024;40(9):961-966
Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis and molecular charac-teristics desmoid fibromatosis the breast(DFB).Methods The clinicopathological data and prognostic information of 26 pa-tients with desmoid fibromatosis of the breast were collected.Their clinical characteristics,histological morphologies,immu-nophenotypes and molecular characteristics were analyzed.Re-sults All the 26 patients were female,with a median age of 34.5 years and an average age of 36.8 years(range from 13 to 69 years).There were 10 cases in left breast,14 cases in right breast and 2 cases in bilateral breast.Isolated and painless breast masses were found in all patients,and 3 cases were ac-companied by nipple depression.Grossly,most of them showed a poorly circumscribed tan-white to gray mass with a trabeculated appearance.Microscopically,all the tumors were composed of mild spindle cells with varying intervals of collagen fiber bun-dles.The boundary between the tumor and the surrounding breast tissue was not clear,and the tumor cells infiltrated adja-cent tissues,such as breast ducts,lobules,adipose tissue,and skeletal muscle.Uniform spindle or oval cells formed in fascicles and interwoven,without atypical or polymorphism;the nuclear chromatin was sparse or vacuolar,with small nucleoli,but mito-ses were rare or absent.Nuclear accumulation of β-catenin was present in 20 of 26 tumors,SMA was variously positive in 20 of 26,desmin was focally positive in 6 of 26;CKpan,CK5/6,p63,CD34,CD10 and S-100 were all negative.The Ki67 index was 5%-10%.The gene mutations of CTNNB1 exon 3 were found in 18 of 26 by Sanger sequencing,including T41A(83.3%),S45P(11.1%)and S45F(5.6%).Two patients also had familial adenomatous polyposis.Local resection was performed in 23 cases,mastectomy was performed in 2 cases,and one case did not require any additional treatment after core needle biopsy.20 cases were followed up for 1-108 months,and no recurrence occurred.Conclusion Desmoid fibromatosis of the breast is rare,and can mimic breast cancer clinically,ra-diologically and histologically.It should be always considered in differential diagnosis for the spindle cell proliferations of the breast.A diagnosis of DFB can be achieved basing on the typi-cal histopathology,immunohistochemistry,history and gene se-quencing.
3.Genetic diagnosis for a patient with Leydig cell hypoplasia caused by two novel variants of LHCGR gene.
Junke XIA ; Luping LI ; Fuhua DUAN ; Jingjing MENG ; Shuping YAN ; Shenglei LI ; Huayan REN ; Xiangdong KONG
Chinese Journal of Medical Genetics 2020;37(8):819-822
OBJECTIVE:
To explore the genetic basis for a patient with Leydig cell hypoplasia.
METHODS:
Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members.
RESULTS:
The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant.
CONCLUSION
The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.
4.METTL3 regulates expression of pluripotent genes in porcine pluripotent stem cells.
Ziyu MA ; Yahui REN ; Min LING ; Huayan WANG
Chinese Journal of Biotechnology 2018;34(3):369-378
In post-transcriptional mRNA modification, m⁶A has been observed in a wide range of eukaryotes. METTL3, as a component of methyltransferase complex for m⁶A modification, regulates mouse naïve pluripotency and influences mRNA stability, especially affecting the expression level of the key pluripotent transcription factors. To reveal the expression pattern of the porcine METTL3 gene, we analyzed METTL3 expression level in different porcine tissues, somatic cells, and induced pluripotent stem cells (piPSCs) by RT-PCR. To identify the function of METTL3 for regulation of the expression of porcine pluripotent genes, we cloned a 1 859-bp coding sequence of METTL3 and synthesized a shRNA against METTL3. When knocking down METTL3 expression in piPSCs, the cell type of piPSCs became naïve-like morphology, alkaline phosphatase activity was increased, and expression level of pluripotent genes NANOG, OCT4 and LIN28A was significantly elevated. In addition, piPSCs cultured in medium containing 10 mmol/L cycloleucine for 48 h exhibited the similar result as that knocked down METTL3. These findings set the stage for optimization of piPS culture condition and further study on the roles of m6A in piPSCs.