2016年 · 第51卷第04期

At present, G-banding karyotyping technology is still the "gold standard" of cytogenetic prenatal diagnosis, but this technology has the limitation of long cell culture and labor consumption. With the development of molecular cytogenetics, new experimental methods appear constantly, and gradually move towards clinical practice. At present, there are fluorescence in situ hybridization (FISH), fluorescence quantitative PCR (QF-PCR), multiplex ligation dependent probe amplification (MLPA), prenatal liquid chip technology (BACs-on-Beads, BoBs) and other technologies in clinical work. These molecular genetic diagnostic technologies do not need cell culture, have a short analysis cycle, and can quickly detect common chromosome aneuploidy abnormalities in fetuses, showing the advantages of high throughput, speed and easy large-scale development. They have important practical significance for solving the problems of insufficient service capacity and long diagnosis cycle of prenatal diagnosis technology with cytogenetic karyotyping as the mainstream technology. FISH technology uses fluorescence-labeled specific oligonucleotide fragments as probes to hybridize with nucleic acids in chromosomes, cells or tissues according to the principle of complementary base pairing, and performs qualitative or relative localization analysis on the DNA to be tested by fluorescence system detection. Compared with the traditional karyotyping technique, FISH technique has the advantages of rapid and high specificity. Because of its intuitiveness, it has become an effective validation method for many genetic diagnostic techniques, and has a broad application prospect.

polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of childbearing age, with an incidence rate of 5% ~8% of women of childbearing age^[1]Serious threat to women's health and quality of life^[2,3]Moreover, the occurrence of PCOS is often accompanied by different degrees of insulin resistance (IR) and compensatory hyperinsulinemia, hyperandrogenemia, and high LH levels. Some studies have shown that the incidence of IR is 50% ~70%^[4]。 IR is also the core of the pathogenesis of metabolic syndrome. In-depth research on the occurrence of IR is of great significance for clarifying the pathogenesis of PCOS and preventing long-term complications. Insulin mainly exerts biological effects through phosphatoylinositol 3 kinase (PI3K) pathway and mitogen-activated protein kinase (MAPK) pathway. The former mediates the metabolic regulation of insulin, and the latter is related to the promotion of cell division and proliferation by insulin. The two signaling pathways interact with each other. Under normal circumstances, after insulin binds to specific insulin receptors on the cell membrane of target cells, it activates insulin receptor substrate (IRS) 1 and 2, and activates downstream signaling molecules through cascade reactions to exert insulin regulation. Among them, IRS-1 mainly activates MAPK/extracellular signal-regulated kinase (ERK) pathway, while IRS-2 mainly involves in regulating PI3K pathway^[5]。 Studies have shown that PI3K pathway is inhibited and MAPK pathway is abnormally activated when PCOS patients have IR. IRS-1 and ERK, as key signaling molecules of MAPK pathway, have been gradually paid attention to in the study of IR mechanism in PCOS patients in recent years. However, most of the researches on the mechanism of IR are focused on insulin target cells, such as skeletal muscle cells^[6]And fat cells^[7]However, there are few studies on the mechanism of IR in ovarian granulosa cells. The interaction between IR and MAPK pathway in ovarian granulosa cells of patients with PCOS remains controversial. In this study, the expression of IRS-1 and ERK2 proteins and the degree of serine phosphorylation in luteinized granulosa cells of PCOS patients were analyzed to explore the molecular biological mechanism of IR in PCOS patients.

At present, there are many ways of preimplantation genetic diagnosis (PGD) of monogenic diseases, and preimplantation genetic haplotyping (PGH) is used, that is, linkage analysis of genetic markers upstream and downstream of pathogenic gene loci, such as short tandem repeats (STR) or single nucleotide polymorphism (SNP) sites associated with pathogenic sites. If STR association analysis is applied, an individualized STR design must be performed for each monogenic disease and verified by family before it can be used for PGD. This process takes 3 to 4 months and is expensive, and it is limited to specific laboratories. Karyomap gene chip is a chip designed for SNP loci in the whole genome. It can analyze nearly 300,000 SNP loci at the same time, and can perform SNP association analysis of internal or adjacent loci in a gene for a certain pathogenic locus. No individual STR loci need to be designed, thus reducing the waiting time and speeding up the experimental process. Moreover, genome-wide SNP analysis can perform genotyping, which can meet the needs of aneuploidy screening. This gives the Karyomap gene chip a clear advantage in terms of PGD. If a couple has a family history of hereditary diseases, such as congenital adrenal hyperplasia (CAH) or autosomal dominant adult polycystic kidney disease (ADPKD), or other monogenic genetic diseases that can cause serious birth defects, PGD with the Karyomap gene chip and preimplantation genetic screening (PGS) for aneuploidy can be considered. The purpose of this study was to investigate the effectiveness of PGD and PGS using Karyomap gene microarray.

After ideal cytoreductive surgery, platinum-based combination chemotherapy is currently the first-line chemotherapy of choice for epithelial ovarian cancer (ovarian cancer), and most ovarian cancer patients are effective for initial treatment. However, about 70% of patients with advanced ovarian cancer will relapse and metastasize and develop platinum resistance^[1]It has seriously affected the efficacy of chemotherapy, which is also the "crux" of the 5-year survival rate of ovarian cancer patients that has not improved significantly. MicroRNA-21 (miR-21) is one of the important microRNAs (miRNAs) in vivo. By targeting and regulating the expression of various apoptosis-related genes in malignant tumor cells, it promotes the proliferation of malignant tumor cells and resists the apoptosis of malignant tumor cells. It not only participates in the occurrence, development, invasion and metastasis of various malignant tumors, but also is closely related to chemotherapy resistance of malignant tumors^[2,3,4]。 Our research group confirmed in previous studies that miR-21 promotes the proliferation, invasion and metastasis of tumor cells by inhibiting the expression of the target gene PTEN^[5]。 The phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) signaling pathway mediated by PTEN gene is an important anti-apoptotic pathway in vivo, and the abnormal activation of this pathway may be closely related to platinum resistance. In this study, we silenced the expression of miR-21 in cisplatin-resistant cells of ovarian cancer, observed the changes of drug resistance of tumor cells, explored the regulatory role of miR-21 in the abnormal activation of PTEN/PI3K/Akt signaling pathway, and further elucidated the molecular mechanism of cisplatin resistance in ovarian cancer.

Central placenta previa combined with placental implantation (PPA), because placental tissue is attached to the lower uterus and accompanied by implantation, it can penetrate the myometrium, serous layer, and even penetrate the bladder. During delivery, the bladder is difficult to dissociate, the lower uterus is atonic, and the placental dissection surface is bleeding extensively, which can lead to severe postpartum hemorrhage^[1]。 PPA is traditionally managed with placental preservation in situ, or emergency hysterectomy during cesarean section^[2]。 However, the probability of severe complications such as sepsis and late postpartum hemorrhage occurring during the treatment of placenta preservation in situ is 6% ~17%^[3]。 Hysterectomy is considered to be an effective measure to treat refractory postpartum hemorrhage caused by PPA, but patients will permanently lose fertility, and the endocrine function of the ovaries will also be impaired, which will hinder physical and mental health^[4]。

gestational diabetes mellitus (GDM) refers to the first abnormal glucose tolerance occurring during pregnancy, and is one of the common complications during pregnancy. The incidence of GDM in China has reached 17.5%^[1]。 GDM is associated with various adverse pregnancy outcomes such as macrosomia, shoulder dystocia, and neonatal hypoglycemia^[2]。 While working to control blood glucose during pregnancy well, exploring the pathogenesis of GDM has important clinical value for early prevention of GDM. It is currently believed that the onset of GDM is associated with an increased degree of insulin resistance during pregnancy. Studies have shown that the enhancement of innate immune response mediated by Toll-like receptors (TLRs) during pregnancy leads to an increase in insulin resistance. As the first TLR found to be expressed in humans, TLR4 is an important part of the innate immune system. Studies have found that TLR4 is associated with various pregnancy disorders such as intrauterine infection and preeclampsia^[3,4]and found significant enhancement of TLR4 expression in the placenta of patients with early-onset preeclampsia^[5]。 TLR4 and its regulatory pathways are involved in the formation of insulin resistance in liver, fat, skeletal muscle and other tissues, so they play an important role in the pathogenesis of metabolic syndrome manifested by type 2 diabetes, hypertension, obesity, etc. Recent studies have found that TLR4 can also aggravate the degree of insulin resistance in GDM patients and play an important role in the pathogenesis of GDM^[6]。 This article mainly expounds the relationship between TLR4 and GDM pathogenesis.

Endometrial cancer is a common malignant tumor of the female reproductive system. Most patients with endometrial cancer are diagnosed in the early stage (stage I), and the overall survival rate of stage I patients is 85% ~91%; However, the prognosis of advanced stage (stage Ⅱ ~ Ⅳ) patients, especially those with adverse pathological features, is worrying, and the 5-year survival rate is only 25% ~30%^[1,2]。 lymph node metastasis (LNM) is the most important prognostic factor in early endometrial cancer^[1,3]Based on the pathological staging principle of endometrial cancer surgery by the International Federation of Obstetrics and Gynecology (FIGO) in 2014, staged surgery should include systemic lymph node dissection (LND), that is, pelvic LND and para-abdominal aortic LND, in addition to total hysterectomy + bilateral adnexectomy^[4]。

Endometrial cancer is a common malignant tumor of female reproductive system, and its incidence has ranked first among gynecological malignant tumors in the United States and Beijing, Shanghai and other regions in China. Because most patients with endometrial cancer have typical symptoms such as abnormal vaginal bleeding in the early stage and are diagnosed in the early clinical stage, the proportion of patients with surgical pathological stage I in 2009 by the International Federation of Obstetrics and Gynecology (FIGO) is very high, accounting for 73.1% ~73.7% according to domestic and foreign data^[1]。 For the treatment of stage I endometrial cancer, the National Comprehensive Cancer Network (NCCN) guidelines recommend total hysterectomy and bilateral adnexectomy + pelvic lymphadenectomy, plus para-aortic lymphadenectomy if there are high risk factors^[2]。 However, there is great controversy about whether patients with stage I low-risk endometrial cancer need lymph node resection, and there are great differences in treatment between different countries, different clinical centers and different doctors. This article discusses whether lymph node resection is necessary for stage I low-risk endometrial cancer.

Editor's note:In June, 2015, Shen Yang and other authors wrote an article on "Related Issues of Paraaortic lymph node dissection for Endometrial Cancer" and submitted it to this journal. This article comprehensively analyzed the risk factors and lymph node metastasis of endometrial cancer, and recommended that the reasonable surgical method for early endometrial cancer for paraaortic lymph node dissection (LND) should be as follows: for patients with low risk of lymph node metastasis (LNM), there is no need to perform para-aortic LND; For patients with high risk of LNM, para-abdominal aortic LND should be performed, with the purpose of comprehensive staging and guiding postoperative adjuvant therapy to improve the prognosis of patients. It reflects the basic views on this issue at home and abroad at present, but some experts have put forward different opinions. Therefore, this journal invited Professor Wen Hongwu to discuss "Does stage I low-risk endometrial cancer need lymph node resection?" Through reviewing the literature and analyzing it, it is proposed that stage I low-risk endometrial cancer can not remove lymph nodes because of the low LNM rate and the insignificant improvement of prognosis after lymph node resection. In view of the above two views, this journal invited famous professors in China to comment.