2018年 · 第53卷第02期

China's cancer statistics show that in 2015, there were 52,100 new cases of ovarian epithelial cancer (ovarian cancer) and 22,500 deaths. Due to the hidden onset of ovarian cancer and the lack of effective early screening methods, early diagnosis and early treatment are extremely difficult. 70% of patients are advanced when they see a doctor, which is a malignant tumor of the female reproductive system with the highest mortality rate^[1]。 The treatment of advanced ovarian cancer is mainly supplemented by surgery and chemotherapy. Chemotherapy plays an important role in the treatment of advanced ovarian cancer. According to the purpose of treatment, chemotherapy can be divided into neoadjuvant chemotherapy (NACT), adjuvant chemotherapy and palliative chemotherapy. For a long time, primary debulking surgery (PDS) and 6 to 8 courses of adjuvant chemotherapy after surgery have been considered as the standard treatment options for advanced ovarian cancer. So far, this treatment model is still respected by the United States. Of course, special circumstances are often encountered clinically. For example, for ovarian cancer patients with large tumors and unable to be operated immediately, the National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommend the application of NACT (Class I evidence) first and then interval debulking surgery (IDS)^[2]。 In 2017, a study from Mexico^[3]It shows that patients with stage IIIC ~ IV ovarian cancer who receive NACT + IDS are more likely to achieve satisfactory tumor reduction surgical results, and the complete resection rate of their tumors (i.e., no residual foci in the naked eye) is as high as 64.5%, while the complete resection rate of PDS is only 35.5%; The incidence of complications such as surgical site infection, deep vein thrombosis, pneumonia, and pulmonary embolism was 8.7%, 5.1%, 2.7%, and 0 in patients receiving NACT + IDS, respectively, which was lower than that in patients receiving PDS (12.7%, 8.9%, 2.7%, and 1.7%, respectively). After years of clinical practice exploration, the efficacy of NACT in patients with advanced ovarian Cancer has been fully affirmed, and it has also been recommended by authoritative academic organizations such as FIGO, NCCN, European Society of Medical Oncology (ESMO) and International Gynecologic Cancer Society (IGCS). However, there are still many controversial issues about the application of NACT in clinical practice, and there is no international consensus yet. This article will elaborate these issues, aiming at arousing the attention and thinking of the majority of gynecological oncologists, and promoting the rational application and clinical research of NACT.

With the adjustment of China's "two-child" policy, the number of pregnant women in the elderly age (≥35 years old) has increased rapidly. According to literature reports, the rate of chromosome abnormality in fetus of older pregnant women is 4.33%, and it increases significantly with the increase of pregnant women's age^[1]。 The reason for fetal genetic defects caused by advanced pregnancy is that with the increase of age, the aging of oocytes of pregnant women, and the influence of harmful environmental factors easily causes chromosomes not to separate or aberrate when germ cells divide. At present, there are many methods for prenatal screening and diagnosis in China. Therefore, some elderly pregnant women who are unwilling or unsuitable for invasive prenatal diagnosis can choose maternal serological screening, non-invasive prenatal testing (NIPT) and other technologies, but invasive prenatal diagnosis is still an irreplaceable method^[2]。 Karyotype analysis has been the "gold standard" of prenatal diagnosis in the past^[2]However, traditional chromosome karyotype analysis cannot correctly judge the small changes of chromosomes (≤5 Mb). chromosome microarray analysis (CMA) can detect the whole genome copy number variation (CNV) of chromosomes, but there are problems such as long reporting waiting time, high cost, and the CNV results of variants of unknown significance (VOUS) cannot be well explained. However, bacterial artificial chromosome microbeads (BoBs) technology can not only quickly and correctly judge the chromosome aneuploidy of common chromosomes (13, 18, 21, X and Y)^[3]It can also directly detect nine common pathogenic microdeletion syndromes. In order to further understand the chromosome abnormalities of elderly pregnant women and provide more detailed prenatal diagnosis information for the clinic, the results of prenatal BoBs detection of 1 980 elderly pregnant women treated in Jinhua Maternal and Child Health Hospital in Zhejiang Province are analyzed and reported as follows.

The thickness of fetal neck translucency (NT) refers to the maximum thickness between the skin and the subcutaneous soft tissue in the sagittal section of the fetal cervical spine level, that is, the thickness of fluid accumulation in the subcutaneous tissue of the posterior part of the fetal neck, which appears as an anechoic zone in the subcutaneous tissue of the posterior part of the fetal neck in ultrasound images. Studies show that the thickness of fetal NT is closely related to its chromosome abnormalities and structural abnormalities^[1]。 However, the previously established NT thickness model is a percentile model, and the percentile is a semi-quantitative scoring method, which cannot accurately evaluate NT thickness. The Z-score model is a quantitative scoring method, which quantitatively reflects the degree to which a specific parameter is higher or lower than the mean of a specific population in multiples of standard deviation (SD). In this study, SonoNT, a semi-automatic ultrasound technique for measuring NT thickness, was used to measure fetal NT in the first trimester of pregnancy. The Z-score model of NT thickness of normal singleton fetus was established, and the data of various abnormal fetuses were compared and analyzed, so as to more accurately and quantitatively assess fetal NT thickness and provide more information for obstetricians.

Hereditary thromboembolism refers to venous thromboembolism (VTE) that is prone to thrombosis due to genetic factors. The causes include coagulation factor V gene mutation, prothrombin gene mutation, protein S deficiency, protein C deficiency, antithrombin (AT) III deficiency, abnormal fibrinogenemia, etc. AT Ⅲ deficiency is autosomal dominant inheritance. AT Ⅲ gene is located in the long arm of chromosome 1, and contains 7 exons and 6 introns, presenting a family inheritance. In this study, three female patients in a family with AT Ⅲ deficiency admitted to Peking Union Medical College Hospital with a total of 7 pregnancy histories (including 2 pregnancy loss caused by thrombosis) were analyzed clinically in this family with AT Ⅲ deficiency complicated with pregnancy, so as to explore the clinical manifestations and management methods of pregnancy in such patients.

Congenital absence of vaginal system embryos are disturbed by internal or external factors during development, resulting in abnormal development of paramesonephric duct; Most patients showed normal vulva, vaginal absence, primary amenorrhea, and normal development of secondary sexual characteristics^[1]。 The incidence of congenital vaginal absence reported abroad is 1/4 500^[2]Domestically, it is up to 1.9%^[3]； The patient had no menstrual cramps during puberty, no vagina or difficulty in sexual intercourse after marriage was found on gynecological examination and went to the doctor. Peritoneal vaginoplasty is one of the commonly used methods for treating congenital absence of vagina.

The incidence of spontaneous abortion is about 15%, and more than two consecutive spontaneous abortions are called recurrent spontaneous abortion (RSA)^[1]。 Chromosomal abnormalities are the most common cause of RSA, and more than 50% of abortions are associated with chromosomal abnormalities in embryos^[2,3]。 In vitro culture of villi or embryonic tissue is commonly used to prepare metaphase chromosomes for genetic diagnosis and to analyze whether there are chromosome abnormalities in aborted embryos. However, cell culture karyotype analysis technology has the characteristics of long cell culture, easy contamination and high requirement of sample collection^[4,5,6]。 2013, American College of Obstetricians and Gynecologists (ACOG) and Society of Maternal-Fetal Medicine (SMFM) Guidelines were published to recommend the use of molecular karyotyping to detect embryo or fetal tissue specimens (amniotic fluid, placenta or abortion tissue) when performing cytogenetic analysis of fetal death intrauterine and stillborn fetuses to improve detection rate^[7]。 In recent years, bacterial artificial chromosomes-on-beads (BoBs) technology based on liquid-phase chip technology has been developed abroad for the detection of abortion tissues, which can quickly and accurately detect the deletion and duplication of long and short arms of chromosomes. This study discusses the feasibility of karyotype BoBs technology for the genetic diagnosis of spontaneous abortion. The results are reported as follows.

Pregnant woman 39 years old, pregnant 5 birth 1, due to "menopause 34 weeks⁺⁵Upper abdominal discomfort for 10 d and aggravation for 4 h "was transferred to the Third Hospital of Peking University. Regular prenatal examination was performed in another hospital, and the gestational age was accurately checked in the first trimester; 33 weeks of gestation⁺²Upper abdominal discomfort occurred at night without obvious trigger, which relieved itself in the morning, and was not diagnosed and treated; 34 weeks gestation⁺⁴The blood pressure was measured at 160/110 mmHg (1 mmHg =0.133 kPa) and the platelet count was 77×10⁹/L, urine protein (+), obstetric ultrasound showed fetal size at 32 weeks gestation⁺²"Severe preeclampsia; HELLP syndrome?" Hospitalization was recommended, and the pregnant woman refused. 34 weeks gestation⁺⁵He had unbearable upper abdominal pain, unable to lie down, and headache. Blood pressure (108~118) / (72~81) mmHg was measured in an outside hospital, and platelet count was 77×10⁹/L, the emergency department was transferred to our hospital. The pregnant woman was in good health in the past and denied a history of hypertension and hepatitis. On admission, blood pressure was measured at 120/90 mmHg, consciousness was clear, no fever, no cardiopulmonary abnormalities, obvious tenderness under the xiphoid process, positive percussion pain in the liver area, and no edema in both lower limbs. Obstetric examination: uterine height 32 cm, abdominal circumference 90 cm, fetal orientation occipital left anterior position (LOA); The baseline of fetal heart rate monitoring was 140 beats/min, with fine variation and no accelerated response, and repeated variation and deceleration were seen. Check the platelet count as 62×10⁹/L, alanine aminotransferase (ALT) 124 U/L, aspartate aminotransferase (AST) 123 U/L, lactate dehydrogenase (LDH) 400 U/L, total bilirubin (TBIL) 27.7 μ mol/L, urine protein (+ +). Admission diagnosis: intrauterine pregnancy, pregnancy 5 delivery 1, LOA; Severe preeclampsia? HELLP syndrome? Fetal distress. After admission, cesarean section of the lower uterine segment was performed in the emergency department. The newborn had a birth weight of 1 730 g, a length of 42 cm, no asphyxia, and was transferred to the neonatology department due to premature birth. During cesarean section: peritoneal blue staining, 850 ml of intraperitoneal free blood; The placenta was not embossed. A dark red blood clot was found on the lower edge of the liver, and a hematoma was seen between the right upper edge of the liver and the diaphragm by bedside ultrasound, about 3.2 cm wide. Laparoscopic exploration showed subcapsular hematoma on the diaphragmatic surface of the liver, mainly in the right lobe, occupying about 2/3 of the diaphragmatic surface of the right liver. The capsule at the diaphragmatic-visceral junction at the lower edge of the right lobe of the liver was partially ruptured, showing a fish's mouth shape, with an extent of about 5 cm, and local bleeding was obvious. Ask the surgeon to consult if there is no active bleeding after compression and hemostasis, and an indwelling abdominal drainage tube is placed. Intraoperative bleeding of 1 000 ml, transfusion of suspended red blood cells for 4 U. The pregnant women were transferred to ICU after operation, and were treated with liver protection and blood pressure reduction, and their vital signs were stable; Transaminases were gradually decreased, and postoperative abdominal ultrasound showed that the liver hematoma was gradually absorbed, and he was discharged from hospital 10 days after operation.

Pregnant woman 26 years old, pregnant 1 delivery 0, due to "menopause 40 weeks⁺⁶He was admitted to our hospital on April 6, 2014 with abdominal pain for 4 h. The blood potassium and magnesium levels were normal during regular physical examination every year in the past. 12 weeks of pregnancy⁺⁶At the first visit to our hospital, there was no early pregnancy reaction, no numbness and fatigue of hands and feet, normal blood pressure, blood potassium level was 2.4 mmol/L (normal range: 3.5~5.1 mmol/L), blood magnesium level was 0.57 mmol/L (normal range: 0.70~1.00 mmol/L), and there was no obvious abnormality. He denied taking diuretics and laxatives. Color ultrasound examination at 23 weeks of pregnancy showed that the fetal heart developed abnormally and there was a single umbilical artery. Serological screening for Down syndrome in the first trimester was low risk, and chromosome analysis of amniotic fluid cell culture was not performed. During pregnancy, the serum potassium level was 2.2-2.6 mmol/L and the serum magnesium level was 0.51-0.67 mmol/L when oral potassium supplementation was treated at 2.0 g/d occasionally. 40 weeks gestation⁺⁶Admission physical examination: muscle strength of limbs was normal, blood pressure and heart rate were normal; Metabolic alkalosis. Electrocardiogram showed T wave changes in some leads, with serum potassium levels ranging from 2.3 to 3.2 mmol/L and serum magnesium levels ranging from 0.64 to 0.80 mmol/L at 40 weeks of pregnancy⁺6 Natural birth of a baby girl. The newborn had a birth weight of 3 595 g, a 1-minute Apgar score of 10, and was admitted to the neonatology department with a blood magnesium level of 0.59 mmol/L; Color ultrasound showed: anomalous pulmonary vein drainage (mixed type, supracardiac + subcardiac type), right aortic arch, pulmonary hypertension; He died of heart failure 7 d after birth. The urine calcium level of pregnant women was 0.3 mmol/L (normal value 2.5-7.5 mmol/L) after discharge from the hospital in the endocrinology department of another hospital. The homozygous mutation of exon 7 c.791C>G (p.A264G) of SLC12A3 gene was revealed by genetic detection, and Gitelman syndrome was diagnosed. The blood potassium levels of the pregnant woman's parents, one sister, one brother, and spouse were all normal, and no genetic test was performed.

The 27-year-old patient was pregnant 2 and gave birth 1. She went to another hospital for "35 d of menopause and 8 h of abdominal pain after intercourse". Ultrasound examination in the other hospital revealed that there was no gestational sac in the uterine cavity, and the right adnexal mass was 4.5 cm ×4.4 cm. Ectopic pregnancy mass was not excluded, and pelvic effusion was 5.3 cm ×2.6 cm. Blood hCG was 314 U/L; Considering "corpus luteum rupture in pregnancy, ectopic pregnancy is not excluded", laparoscopic right ovarian corpus luteum rupture repair + pelvic adhesion release + diagnosis and curettage were performed under general anesthesia; The results of postoperative pathological examination were as follows: endometrium and interstitial decidual change in secretory phase, right ovarian corpus luteum cyst rupture and bleeding; The reexamination blood hCG was 420 U/L, and the diagnosis was ectopic pregnancy; After that, methotrexate 20 mg was injected intramuscularly for 5 consecutive days.

The 37-year-old patient received a one-time intramuscular injection of methotrexate 80 mg in an external hospital on February 1, 2016 due to "ectopic pregnancy", and developed nausea and vomiting the next day; On day 4, serum creatinine (SCr) was 622.0 μ mol/L, urea nitrogen (BUN) 13.47 mmol/L, alanine aminotransferase (ALT) 40.0 U/L, aspartate aminotransferase (AST) 43.4 U/L, and blood routine showed white blood cell count (WBC) 7.59×10⁹/L, hemoglobin (Hb) 94 g/L, platelet count (PLT) 214×10⁹/L; No decrease in urine volume was observed during the course of the disease, approximately 2 000 ml per day. Previous history of chronic hepatitis B with unknown renal function prior to medication. Day 6 SCr 689.2 μ mol/L, BUN 21.16 mmol/L, ALT 94.8 U/L, AST 100.3 U/L, WBC 9.46×10⁹/L, Hb 89 g/L, PLT 207×10⁹/L, the femoral vein catheter was temporarily placed after the informed consent form was signed, and intermittent high-flux hemodialysis was performed with blood flow of 200 ml/min, dialysate flow of 500 ml/min, and low molecular weight heparin 3 000 U anticoagulation. On the 7th day, multiple oral ulcers and skin ulcers began to appear; Because the patient had acute hematopoietic arrest, the bone marrow puncture examination report showed decreased granulocyte, erythroid and megakaryocyte proliferation. On the 12th day, the serum methotrexate concentration was measured at 0.422 μ mol/L, and the heparin dosage was continuously adjusted. The heparin dosage was transferred to the laminar flow ward of the hematology department for bedside intermittent venous-venous high-flux hemodialysis treatment. The hemodynamics were stable during the dialysis process. On day 24, no dialysis was performed for 2 days, but SCr decreased to 152.6 μ mol/L and BUN was 25.03 mmol/L, and dialysis was stopped; ALT 23.3 U/L, AST 13.0 U/L, WBC 3.97×10⁹/L, Hb 71 g/L, PLT 69×10⁹/L, and the plasma concentration of methotrexate was 0.015 μ mol/L. Plasma concentrations of methotrexate gradually decreased and were undetectable by day 32. During the course of the disease, the patient developed severe gastrointestinal mucosal lesions, hepatic impairment and severe infection. Calcium leucovorin was given for rescue on day 11; During the course of the disease, liver protection, biapenem and teicoplanin were given as anti-infective treatment. Day 32, re-examination SCr 80.6 μ mol/L, BUN 8.41 mmol/L, ALT 32.9 U/L, AST 23.9 U/L, WBC 11.42×10⁹/L, Hb 87 g/L, PLT 350×10⁹/L. On the 126th day, the liver and kidney function and blood routine results were all normal. On the 26th day, MTHFR gene 667C>T locus was TT genotype, suggesting mutant homozygous, MTHFR gene 1298A>C locus was AA genotype, suggesting wild homozygous, and GSTP1 gene 313A>G locus was AA genotype, suggesting wild homozygous.

The intestinal microecosystem, as a complex and important "functional organ", colonizes 1×10¹⁴A microorganism encoding 3.3 million genes. Intestinal flora participates in many important physiological functions such as nutrient absorption, energy metabolism, immune defense and endocrine regulation through its genes, intermediate products and metabolic ability, and plays a vital role in maintaining intestinal barrier function, immune regulation and even long-term health of the body. Following the launch of the human microbiome project (HMP) study by the National Institutes of Health (NIH) in December 2007, in May 2016, the U.S. government launched a new National microbiome initiative (NMI) to establish the healthy microbiome as one of the research objectives. In the field of obstetrics, the changes and functions of maternal intestinal microecology in normal pregnancy, how to participate in the occurrence and development of pathological pregnancy, and then affect maternal health and fetal development, will be hot issues faced by obstetric researchers, and at the same time, it brings new opportunities for the long-term health research of mothers and offspring.

Endometriosis (endometriosis) refers to the appearance of endometrial tissue (glands and interstitium) with growth function in sites other than the endometrium and myometrium, and the occurrence of periodic bleeding; It is a common disease in women of childbearing age, and the pain symptoms caused by it are one of the important reasons that affect the quality of life of patients. endometriosis associated pain is a type of neuropathic pain, that is, pain caused by damage or lesions in the peripheral or central nervous system. Endometriosis-related pain is closely related to the damage and regeneration of nerve fibers, inflammatory microenvironment, dysfunction of sex hormones and neuroangiogenesis in endometriosis lesions. high mobility group protein box 1 (HMGB1) was found to be expressed at elevated levels in endometriosis^[1,2,3,4], suggesting that it may be involved in the pathophysiological mechanism of endometriosis. HMGB1 can be released into the extracellular stroma and play a variety of biological roles, one of which is to regulate the growth of nerve axons and participate in the occurrence of neuropathic pain. However, whether HMGB1 is involved in the occurrence of endometriosis-related pain remains to be further investigated. This paper analyzes the potential mechanism of HMGB1 involvement in neuropathic pain in endometriosis from different perspectives.

Endometrial cancer is a common malignant tumor of the female reproductive system. In 2016, there were 61,380 new cases of endometrial cancer in the United States, second only to breast cancer, lung cancer and colorectal cancer, ranking fourth among female malignant tumors, much higher than 12,820 new cases of cervical cancer and 22,440 new cases of ovarian epithelial cancer. And in 2016, 10,920 patients died of endometrial cancer in the United States, ranking 6th in female malignant tumor deaths^[1]。 The incidence of endometrial cancer in China is also increasing year by year. Lymph metastasis is the main metastatic route of endometrial cancer. Traditional staging surgery includes pelvic lymph node and para-aortic lymph node resection, but the surgical complications brought by it seriously affect the quality of life of patients. With the emergence and development of sentinel lymph node (SLN) tracing technology, a variety of selection strategies for lymph node resection have been proposed. In order to understand the value of SLN detection in endometrial cancer surgery and the new progress of the factors affecting SLN detection, this paper reviews the recent literature as follows.

In 2014, the Obstetrics Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association referred to the expert consensus of the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM)^[1]Published the "Expert Consensus on Standards and Treatment of New Labor Process (2014)" (abbreviated as: Expert Consensus on New Labor Process)^[2]It has attracted widespread attention from domestic obstetricians and midwives^[3]。 After more than three years of clinical practice, obstetricians and midwives still have some confusion and controversy in the face of the "new labor process expert consensus"^[4]。 Therefore, the Obstetrics Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association and the Perinatal Medicine Branch of the Chinese Medical Association believe that it is necessary to make an in-depth understanding and explanation of the "new labor expert consensus", so as to guide obstetricians and midwives to better apply the "new labor expert consensus".