Ameliorative effect of myo-inositol on red blood cell alterations in polycystic ovary syndrome: in vitro study

Polycystic ovary syndrome (PCOS)is a gynecological endocrine disorder which is associated with systemic inflammatory status inducing red blood cells (RBC) membrane alterations related to insulin resistance and testosterone levels which could be greatly improved by myo-inositol (MYO) uptake. In this study we aim to evaluate the effect of MYO in reducing oxidative-related alterations through in vitro study on PCOS RBC. Blood samples from two groups of volunteers, control group (CG, n?=?12) and PCOS patient group (PG, n?=?12), were analyzed for band 3 tyrosine phosphorylation (Tyr-P), high molecular weight aggregate (HMWA), IgG in RBC membranes, and glutathione (GSH) in cytosol, following O/N incubation in the presence or absence of MYO. PCOS RBC underwent oxidative stress as indicated by higher band 3 Tyr-P and HMWA and increased membrane bound autologous IgG. Twenty four hours (but not shorter time) MYO incubation, significantly improved both Tyr-P level and HMWA formation and concomitant membrane IgG binding. However, no relevant modification of GSH content was detected. PCOS RBC membranes are characterized by increased oxidized level and enhanced sensitivity to oxidative injuries leading to potential premature RBC removal. MYO treatment is effective in reducing oxidative related abnormalities in PCOS patients probably restoring the inositol phospholipid pools of the membranes.     

Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries

Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture.     

Initiation of human parturition. III. Fetal membrane content of prostaglandin E2 and F2alpha precursor.

Unesterified arachidonic acid is the obligatory precursor of the prostaglandins (PG), PGF2alpha and PGE2. In order to ascertain whether or not the human fetal membranes could represent a storage site for prostaglandin(s) precursor, the fatty acid content of human fetal membranes was measured. Approximately 20% of the fatty acids found in fetal membranes obtained from near-term, non-laboring women was arachidonic acid, whereas only 0.4% of the fatty acids of the parietal peritoneum of the mother is arachidonic acid. A small but significant decrease in the arachidonic acid concentration was found in the fetal membranes obtained from laboring women compared to that found prior to labor. On the other hand, the concentration of palmitic acid was increased in membranes obtained during labor while no significant changes in concentration in the remaining fatty acids were observed in membranes from laboring compared to non-laboring near-term gravidas. The significance of these observations in relation to the availability of prostaglandin precursor and the initiation of human parturition is considered.     

Lewis phenotype in women with preterm labor and premature rupture of the membranes

Objective: The purpose of this study was to evaluate the possible association between Lewis phenotype status in pregnant women and preterm labor (PTL) or preterm rupture of the membranes (PROM).Methods: Red blood cell (RBC) Lewis phenotype was determined in 113 pregnant women admitted for PTL or PROM and in 121 controls. The results were controlled for the influence of race on Lewis phenotype.Results: Pregnancy was associated with a higher frequency in women with the a-b- phenotype. There was no association between RBC Lewis phenotype and the occurrence of PTL or PROM.Conclusions: A susceptibility to PTL or PROM is not due to a lack of Lewis antigen expression on the plasma membrane of the vaginal mucosa.     

Linoleic and arachidonic acid in perinatal asphyxia and prematurity.

OBJECTIVES: Long-chain polyunsaturated fatty acids (LC-PUFA) are important for fetal and infant growth and development. The effects of prematurity and perinatal asphyxia on the levels of linoleic acid (LA) and arachidonic acid (AA) in plasma and red blood cell (RBC) membranes were investigated. METHODS: Fifty-five neonates were studied: 18 full term neonates with perinatal asphyxia (group A), nine preterm neonates (group B), and 28 healthy term neonates (group C). Non-esterified and total levels of LA and AA in plasma and RBC membranes were estimated using gas chromatography within the first day of life. Malondialdehyde (MDA) levels were measured using the thiobarbituric acid (TBA) reactivity method. RESULTS: Compared to group C, statistically significant lower levels of plasma free and total AA and free LA were observed in group A, whereas statistically significant higher levels of RBC total LA and AA were observed in RBC membranes of group B. A negative correlation between MDA and LC-PUFA levels was found. CONCLUSION: Perinatal asphyxia is associated with a reduction in LC-PUFA levels, most likely as a result of increased oxidative stress. Premature infants soon after birth have higher LC-PUFA levels than term neonates, probably reflecting the overall metabolic activity and/or intrauterine transport of LC-PUFA.     

Susceptibility of red blood cell lipids to in vitro oxidation and antioxidant status in preeclampsia

Objective

To investigate susceptibility of red blood cell (RBC) lipids to oxidation and antioxidant status in preeclampsia.

Study design

Twenty-one women with mild preeclampsia, 21 women with severe preeclampsia, and 20 healthy pregnant women were included in this cross-sectional study. Susceptibility of RBC to oxidative stress was determined by measuring RBC-malondialdehyde levels after incubation with hydrogen peroxide. Vitamins E and C, total carotenoids and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) activities and serum total antioxidant capacity (TAC) were determined spectrophotometrically. One-way analysis of variance and correlation analysis were used for statistical analyses.

Results

Compared with the normal pregnant women, susceptibility of RBC to oxidation was enhanced in the mild (p < 0.05) and severe (p < 0.01) preeclampsia groups, TAC was lower in the mild (p < 0.01) and severe (p < 0.001) preeclampsia groups. Vitamin C level was decreased in severe preeclampsia and total carotene level was decreased in mild and severe preeclampsia groups (p < 0.05). GPx activity was also decreased in the mild (p < 0.01) and severe (p < 0.05) preeclampsia groups.

Conclusion

The results of the present study supported the oxidative stress hypothesis of preeclampsia and it is possible that RBC play a role in the pathophysiology of the disease.     

Identification of anti-syntaxin 5 autoantibody as a novel serum marker of endometriosis

The sensitivity and specificity of CA125, as a sole serum marker of endometriosis, are not high enough for routine clinical assessment. To explore new markers for the diagnosis of endometriosis, serum autoantibodies in endometriotic patients were investigated employing a fibroblast cell line, two-dimensional (2D) gel electrophoresis and Western blotting. Proteins reacting with serum autoantibodies by Western blotting were identified using MASCOT analysis. ELISAs were then prepared using recombinant proteins and titers of serum autoantibodies were determined in the endometriotic patients, disease controls, and healthy subjects. Among the autoantibodies identified, anti-syntaxin 5 (STX5) autoantibody levels were significantly elevated in endometriotic patients. Sensitivity (53.6%) and accuracy (72.2%) of the serum anti-STX5 autoantibody assay were better than those of serum CA125 levels (36.2% and 62.9%, respectively) for diagnosis. The sensitivity of anti-STX5 autoantibody was remarkably high in Stage II (80.0%) compared with that of CA125 (40.0%). A combination assay of anti-STX5 autoantibody with CA125 improved the overall sensitivity to 69.6%. We conclude that serum anti-STX5 autoantibody, which was discovered by a proteomic approach, is a potential new serum marker for the diagnosis of endometriosis. This initial study now requires validation by further clinical evaluation.     

Classification of ovarian endometriotic cysts.

Current literature describes 3 different pathogenetic types of ovarian endometriotic cysts. Cortical invagination cysts arise when surface ovarian endometriotic deposits adhere to another structure (such as the broad ligament), blocking the egress of menstrual fluid produced by cycling endometriosis, which then collects and causes the ovarian cortex to invaginate. Surface inclusion cyst-related endometriotic cysts develop when endometriotic tissue colonizes preexisting inclusion cysts. Physiological cyst-related endometriotic cysts occur when endometriosis gains access to a follicle, such as at the time of ovulation. To determine whether routine histological examination is of use in the classification of endometriotic cysts, and if so, whether such classification is of clinical relevance, we reviewed the histology of endometriotic cysts of 29 women under 35 years of age. Young women were chosen so that ovarian cortex surrounding the endometriotic lining in invagination cysts could be identified by the finding of oocytes. Ten women (34%) had cortical invagination endometriotic cysts, but no inclusion or physiological cyst-related endometriomas were found. The remaining 19 women (66%) had unclassified endometriotic cysts, of which 14 (48% of total) had a fibrous wall between the endometriotic lining and medulla and 5 had extensive destruction of ovarian tissue. We concluded that cortical invagination cysts were the only common diagnosable sort of the 3 types currently being investigated and that unclassified cysts required further study to determine their pathogenesis. Our study highlights the need for a prospective study using standardized pathological and clinical methods.     

Apoptosis pattern in human endometrium in women with pelvic endometriosis

OBJECTIVE: In the present study we aimed to describe apoptosis patterns in eutopic endometrium in women suffering from endometriosis in order to assess its value as a marker of early forms of endometriosis, and also to try to answer whether endometriosis is caused by changes within the eutopic endometrium or whether endometriotic lesions change the characteristics of eutopic endometrium. STUDY DESIGN: The study was performed on 125 women treated in Division of Reproduction. In 52 patients peritoneal endometriosis was diagnosed (I(0)-23; II(0)-29). Seventy-three patients in whom no endometriotic foci could be found at laparoscopy were qualified as the control group. Endometrial biopsy 7-9 days after ovulation was taken for assessment of apoptosis (TUNEL) and routine histology. RESULTS: Apoptosis indices in the eutopic endometrium of women with endometriosis were lower compared to women without endometriosis. In the endometrial glands apoptosis indices were 2.94+/-1.66 versus 5.23+/-2.06 (p<0.01) in the group of women with and without endometriosis, respectively. In the endometrial stroma apoptosis indices were estimated at 2.04+/-1.72 in women with endometriosis and 4.12+/-1.62 in the control group (p<0.01). CONCLUSIONS: The observed changes could support the hypothesis of the different properties of eutopic endometrium in endometriotic women as a causing factor of peritoneal endometriosis.     

Altered placental oxidative stress status in gestational diabetes mellitus

Oxidative stress has been clearly linked to type 2 diabetes mellitus, however, limited data are available on the involvement of oxidative stress in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The aim of this study was to investigate the status of placental oxidative stress in healthy pregnant women and women with GDM. The hypothesis to be tested was that tissue markers of oxidative stress are significantly increased in GDM compared to normal placental tissues. Markers of oxidative stress measured were the release of 8-isoprostane (8-epi-prostaglandin F(2alpha)) from human term placental explants (n=11), the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase (n=10), and protein carbonyl content (n=12). Placental release of 8-isoprostane was 2-fold greater from women with GDM (P<0.001) compared to healthy pregnant women. Superoxide dismutase activity and protein carbonyl content were elevated in placentae obtained from women with GDM (P<0.04 and P<0.004 respectively), whilst there was no significant difference in the activity of glutathione peroxidase. These data demonstrate the presence of oxidative stress in the placenta from women with GDM, in addition to the induction of a key antioxidant, collectively indicating a state of existing oxidative stress in this condition.     

左炔诺孕酮宫内缓释系统用于子宫内膜异位症保守性手术后复发的治疗

目的 探讨左炔诺孕酮宫内缓释系统(LNG-IUS)用于子宫内膜异位症(内异症)患者保守性手术或保守性手术联合药物巩固治疗后复发者治疗的效果.方法 选择因内异症复发而就诊的患者23例,于月经周期第5～7天宫内放置LNG-IUS.所有患者均无生育要求且不愿再次手术.于放置LNG-IUS后3、6、12、24、36个月随访,观察放置LNG-IUS前后患者疼痛视觉模拟(VAS)评分、血清CA125水平、卵巢内异症囊肿体积的变化以及月经情况、体质量等指标.结果 (1)VAS评分:放置LNG-IUS后12个月,痛经、慢性盆腔痛或性交痛缓解最为明显,VAS评分由放置LNG-IUS前的(5.9±2.3)、(4.3±2.0)分下降为(1.0±0.7)、(1.4±1.1)分,分别比较,差异均有统计学意义(P＜0.01).(2)囊肿体积:11例患者复发表现为卵巢内异症囊肿,放置LNG-IUS后6个月,卵巢内异症囊肿体积由放置前的(11.4±6.1)cm3下降至(5.5±3.4)cm3,两者比较,差异也有统计学意义(P＜0.01);放置12个月时,2例卵巢内异症囊肿消失,放置24个月时,共9例卵巢内异症囊肿消失.(3)血清CA125:从放置LNG-IUS后6个月时开始,CA125水平显著下降,由放置前的(65.5±19.6)kU/L降至放置6个月时的(42.1±13.6)kU/L,差异有统计学意义(P＜0.01),放置后12个月时,CA125水平仍继续下降,此后趋于平稳.(4)其他:放置LNG-IUS后6个月内,阴道不规则出血或点滴出血是常见现象,随着放置时间延长,情况明显缓解.少数患者出现体质量增加的情况.结论 内异症保守性手术或手术联合药物巩固治疗后复发的患者,应用LNG-IUS可有效地缓解疼痛症状,降低血清CA125水平,缩小卵巢内异症囊肿体积,是一种有效、安全、持续时间长、全身副作用少、依从性高的治疗方法.

Abstract：

Objective To evaluate the efficiency of levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of recurrent endometriosis after conservative surgery or conservative surgery combined with medical treatment. Methods Twenty-three patients with recurrent endometriosis after conservative surgery or conservative surgery combined with medical treatment were treated by LNG-IUS. All patients rejected further operation and had no desire of fertility. The visual analogue scale (VAS) scores of pain, menstrual model, weight and serum CA125 level and the volume of ovarian endometriotic cysts before and after 3, 6, 12, 24 and 36 months of treatment were recorded and compared. Results ( 1 ) VAS score:after 12 months of using LNG-IUS, dysmenorrheal, chronic pelvic pain or dyspareunia were relieved significantly. VAS score were dropped from 5.9 ± 2. 3,4. 3 ± 2.0 to 1.0 ± 0. 7,1.4 ± 1. 1 ( P ＜ 0. 01 ). ( 2 )Volum of cysts :after 6 months of using LNG-IUS, the volume of recurrent ovarian endometriotic cysts in 11 patients were reduced from ( 11.4 ± 6. 1 ) em3 to ( 5. 5 ± 3.4 ) em3 significantly ( P ＜ 0. 01 ). At 12 months of follow-up, it suggested that 2 patients' ovarian endometriotic cysts disappeared. At 24 months follow-up,9 patients ovarian endometriotic cysts disappeared ( 3 ) CA125: serum CA125 decreased from ( 65.5 ± 19. 6 )kU/L to (42. 1 ± 13.6) kU/L at 6 months after treatment remarkably (P ＜ 0. 01 ). Continued to decrease after 12 months and then become steady. Irregular bleeding and spotting was the main side effects, weight gain was also observed in few patients. Conclusions LNG-IUS could be used in treatment of recurrent endometriosis after conservative surgery or conservative surgery combined with medical treatment effectively. It could relieve pain, reduce the level of CA125 and decrease the size of ovarian endometriotic cysts. LNG-IUS seems to be an effective, safe, and long term treatment for endometriosis with fewer side effects and better compliance.     

Serum lipid oxidizibility in term premature rupture of the membranes

OBJECTIVE: In our previous studies we have shown that the process of term labor is associated with oxidative stress, as indicated by increased susceptibility of maternal serum lipids to copper induced peroxidation. In order to continue evaluating the role of oxidative stress in the labor process, we next tested whether term premature rupture of the membranes (PROM) is also associated with increased susceptibility of maternal serum lipids to copper induced peroxidation. DESIGN: A controlled prospective study. SETTING: Tertiary care centre. POPULATION: 31 healthy women with term PROM and 19 healthy pregnant women with intact membranes. The women were matched for maternal and gestational age. METHODS: Venous blood was drawn from the women (up to 6h after rupture of the membranes and prior to labor in the PROM group), and the kinetics of copper-induced oxidation of serum lipids ex vivo were monitored spectroscopically at 37 degrees C by continuous recording of absorbance at 245 nm. RESULTS: The lag phase, reflecting resistance of serum lipids to oxidation, was similar in the PROM group when compared to the control group (43.7+/-3.2 versus 41.9+/-1.6 min, P=0.61). However, the maximal rate of oxidation (V(max)) and the maximal accumulation of absorbing products (OD(max)) were shorter in the PROM group when compared to the control group (5.14+/-0.26 versus 6.29+/-0.4010(-3) OD(245) nm/min, P=0.016; 0.61+/-0.03 versus 0.71+/-0.04 OD(245) nm, P=0.07). CONCLUSION: As opposed to term labor, term PROM is not associated with increased maternal systemic oxidative stress when compared to normal pregnant women. The role for oxidative stress in preterm PROM warrants further studies.     

Immunohistochemical localization of insulin-like growth factor-binding protein-3 in eutopic and ectopic endometrial tissues

Objective: To evaluate the expression of insulin-like growth factor–binding protein-3 (IGFBP-3) in the eutopic endometrium and in endometriotic lesions.

Design: Retrospective immunohistochemical study.

Patient(s): Twenty-five normal women and 39 women with endometriosis.

Intervention(s): Endometrial and endometriotic tissue biopsies obtained at laparoscopy.

Main Outcome Measure(s): Expression of IGFBP-3 assessed by immunohistochemistry.

Result(s): In the endometrium, positive immunostaining of IGFBP-3 was observed both in the stroma and the epithelial glands. The intensity of staining in the glands during the secretory phase was significantly higher in women with endometriosis compared with controls (P=.018). An increased expression of IGFBP-3 over controls was found in stages I and II of the disease (P=.018), whereas in stages III and IV, the difference between controls and women with endometriosis was not significant (P=.300). In endometriotic tissues, a much-marked immunostaining of IGFBP-3 was noted in 90% of the glands and 67% of the stroma without apparent differences related to cycle phase.

Conclusion(s): These data show intense staining of IGFBP-3 in endometriosis lesions and increased expression of the protein in the endometrium of patients with endometriosis compared to controls. This marked expression of IGFBP-3 could be related to its previous finding in the peritoneal fluid and to its potential involvement in the pathophysiology of endometriosis.     

CA 125 in serum, peritoneal fluid, active lesions, and endometrium of patients with endometriosis

Ca 125 levels in serum and peritoneal fluid were measured in 39 patients with endometriosis and 18 patients with normal pelvic anatomy at laparoscopy, and the presence of this antigen in endometriotic tissue and endometrial mucosa was also investigated. Serum CA 125 concentrations were elevated in patients with Stage III or IV endometriosis compared with control subjects (32.9 +/- 11.2 versus 16.4 +/- 8.9 U/ml, means +/- SD; p less than 0.001). CA 125 values were greater than 35 U/ml in 36.8% of women with Stage III or IV endometriosis and in none of the control subjects. No significant differences in CA 125 levels in peritoneal fluid were found between patients with endometriosis and control subjects. The immunohistochemical studies found CA 125 in 10% of the endometriotic lesions and 37.5% of the endometrial samples of patients with endometriosis and in 33.3% of the endometrial samples of control subjects.     

Prostaglandin F2 alpha and E2 release by peritoneum with and without endometriosis

Peritoneal endometriotic implants and adjacent normal peritoneum from five patients were analyzed for prostaglandin (PG) release. Each tissue biopsy was incubated using medium 199 in triplicate at 37 degrees C for six hours, and PGF2 alpha and PGE2 concentrations were measured in the incubation medium every two hours. This study demonstrates that peritoneum involved with endometriosis releases significantly more PGF2 alpha and PGE2 (P less than .05) than adjacent normal peritoneum, and suggests that peritoneal endometriotic implants may be a source of the elevated peritoneal fluid PG levels previously reported in patients with endometriosis.     

Fundamental and clinical studies on biochemical properties of endometriosis in comparison with endometrium

1. Regulatory mechanism of cell growth of endometriosis in comparison with endometrium. Estradiol alone has no growth-promoting effect on both endometriotic and endometrial cells. Epidermal growth factor (EGF) stimulates cell growth of both cell types. Endometrial cells but not endometriotic cells produce and release EGF into culture media so that stimulatory effect of exogenous addition of EGF is blunted in endometrial cells. Estradiol exerts its mitogenic action by enhancing the mitogenic effect of EGF in endometrium. By contrast, the effect of estradiol is minimal in endometriotic cells, showing less dependency on estradiol for their proliferation. Progesterone inhibits cell growth of the both cell types in the same manner. 2. A biological role of EGF in endometriosis. Endometriotic cells possess EGF receptors. The affinity of the receptor is the same as that of endometrial cells. However, the number of receptor per cell is about half of that for endometrium. Estradiol increases the number of EGF receptors in endometrial cells which may explain the mitogenic effect of estradiol in the face of EGF. However, stimulatory effect of estradiol for EGF receptors is less pronounced in endometriotic cells. Mitogenic action of EGF is suggested to be mediated by phosphorylation of tyrosine residues of 170 kd protein in the tissues. EGF increases the production of tissue plasminogen activator (t-PA) and activates the aromatase activity of the both cell types. However, the stimulatory action of EGF on progestin receptor is observed only in endometrial cells. 3. Biochemical characterization of endometriotic cells in comparison with endometrial cells. Endometriotic tissues accumulate less amount of glycogen and XIII factor of blood coagulation as compared to endometrial tissues. The ability of endometriotic cells to release prostaglandin is also weaker, suggesting suppressed differentiated function of endometriotic cell. Endometriotic cells produce the same amount of CA125 as endometrial cells. Danazol and EGF inhibit the release of CA125 into culture media when standardized per cell. Therefore, normalization of CA125 levels during the treatment dose not always mean the reduction of the lesions but reflect the suppressed function of the endometriotic tissues. 4. Altered microenvironment of endometriotic tissues. An analysis of peritoneal fluid. The amount of peritoneal fluid (PF) with endometriosis increased throughout the menstrual cycle. A number of macrophage is reported to increase in PF with endometriosis.(ABSTRACT TRUNCATED AT 400 WORDS)     

血清人附睾分泌蛋白4和CA125水平检测在卵巢恶性肿瘤中的诊断价值

目的 探讨血清人附睾分泌蛋白4(HE4)和CA125水平检测在卵巢恶性肿瘤诊断中的价值.方法 用酶联免疫吸附试验方法 对卵巢恶性肿瘤组(30例)、盆腔良性疾病组(110例,其中卵巢良性肿瘤45例、子宫内膜异位症和子宫腺肌病57例和盆腔炎8例)和正常组(137例)妇女血清中HFA和CA125水平进行双盲检测,结果 以中位数表示,分析两指标单独或联合检测诊断卵巢恶性肿瘤的价值.血清HF4和CA125正常值分别为0～150 pmoVL和0～35 kU/L,单独或联合检测时,其中任一指标高于正常值即定为阳性.结果 (1)卵巢恶性肿瘤组血清HE4和CA125水平分别为244 pmol/L 和601 kU/L,分别与盆腔良性疾病组(分别为32 pmoVL和22 kU/L)和正常组(分别为32 pmol/L和11 kU/L)比较,差异均有统计学意义(P<0.05).卵巢恶性肿瘤组血清HE4单项检测的阳性率为63.3%,明显低于血清CA125项榆测的阳性率(86.7%,P=0.036).(2)单项检测时,以盆腔良性疾病组作参照人群时,HE4和CA125单项检测的受试者工作特征曲线下面积(ROC-AUC)分别为0.900和0.840,其特异度为100%时的敏感度分别为70%和7%,两者比较,差异有统计学意义(P=0.000);以正常组作参照人群时,HE4和CAl25单项检测的ROC-AUC分别0.904和0.914,其特异度为100%时的敏感度分别为67%和87%,两者比较,差异有统计学意义(P=0.031).(3)联合检测时,以盆腔良性疾病组作参照人群时,HE4+CA,笛联合检测和CA125单项检测的ROC-AUC分别为0.894和0.840,其特异度为100%时的敏感度分别为50%和7%,两者比较,差异有统计学意义(P=0.000).以正常组作参照人群时,HE4+CA125联合榆测和HE4单项检测的ROC-AUC分别为0.914和0.904,其特异度为100%时的敏感度分别为87%和67%,两者比较,差异有统计学意义(P=0.031).以盆腔良性疾病组作参照人群时,HE4+CA125联合检测在特异度为100%时的敏感度(50%)虽然低于HE4单项检测(70%),但两者比较,差异无统计学意义(P=0.070).(4)以ROC曲线最左上方的点86 pmol/L、正常组95%参考值50 pmoVL和正常值的上限150 pmol/L为界值点,比较HE4单项检测对卵巢恶性肿瘤的诊断能力,结果 显示,界值点为50 pmol/L时的特异度和阳性预测值分别为95%和63%,明显低于界值点为86(分别为100%和95%)和150 pmoVL(均为100%)时的特异度和阴性预测值(P<0.01).结论 HE4单项检测诊断卵巢恶性肿瘤的特异度优于CA125单项检测,两者联合检测可以提高诊断能力.以150 pmol/L为界值点,对卵巢恶性肿瘤的诊断正确率更高,而以86 pmol/L为界值点有利于卵巢恶性肿瘤的筛查、降低漏诊率.