Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway.

Colorectal cancer is the third leading cancer in the world in terms of incidence and mortality. The role of differentially expressed Claudin-14 (CLDN14) in CRC has not been reported. We observed that CLDN14 was associated with the progression of CRC. Our functional studies have shown that CLDN14 promoted the proliferation of CRC cells. In addition, CLDN14 also increased the migration and invasion of CRC cells. In vivo experiments also showed that CLDN14 promoted the growth of colorectal cancer via the PI3K/AKT/mTOR. In summary, our research suggests that CLDN14 promotes the progression of colorectal cancer. Our findings may provide new strategies for clinical management and patient prognosis of CRC.

Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ).

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

Building a predictive model for successful vaginal delivery in nulliparas with term cephalic singleton pregnancies using decision tree analysis.

AIM: To establish a model predicting successful vaginal delivery (VD) in nulliparas with term cephalic singleton pregnancies. METHODS: We retrospectively identified 6799 term nulliparas with cephalic singletons (6416 VD and 383 cesarean section [CS] due to dystocia) who entered labor (cervical dilation ≥2 cm) between September 2014 and August 2015. Using VD as the dependent variable and age, maternal body height, educational attainment, gravidity, gestational age, pre-pregnancy body mass index (BMI), BMI upon admission for delivery, gestational weight gain, gestational hypertension and gestational diabetes as the independent variables, predictors of VD success were identified using a multivariate binary logistic regression and then ranked with decision-tree analysis. RESULTS: While multiple factors are associated with improved VD success, we found body height, gestational age, and intrapartum BMI to be the best predictors of successful VD. Our predictive model has a classification accuracy, sensitivity and specificity of 76.6%, 96.7% and 16.4%, respectively, and it was subsequently confirmed by both internal and external validation. CONCLUSION: Our predictive model indicates body height, gestational age and intrapartum BMI as the major predictors of successful VD in low-risk patients.

Identifying appropriate pre-pregnancy body mass index classification to improve pregnancy outcomes in women of childbearing age in Beijing, China: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: This study explored the appropriate classification of pre-pregnancy body mass index (BMI) in women of childbearing age in Beijing, China. METHODS AND STUDY DESIGN: Women with singleton pregnancies at more than 28 gestational weeks were retrospectively reviewed. Based on the pre-pregnancy BMI (kg/m2), these patients were divided into 7 groups: <18.5, >=18.5-22.9, >=23-23.9, >=24-24.9, >=25-27.9, >=28-29.9, and >=30. Pregnancy adverse outcomes, including gestational hypertension with or without preeclampsia, gestational diabetes mellitus, initial cesarean section, postpartum hemorrhage, macrosomia, large-for-gestational age infant and so on were recorded. Binary logistic regression analysis was used to calculate the uncorrected and corrected odds ratios and 95% confidence intervals, with the >=18.5-22.9 group serving as a reference. RESULTS: A total of 11,136 pregnant women were analyzed. Incidences of above mentioned six adverse outcomes were greater in women with higher pre-pregnancy BMI. The risks of the abovementioned six adverse outcomes were increased significantly among the >=23-23.9, >=24-24.9, >=25-27.9 groups and substantially higher in the >=28-29.9, >=30 groups after correction. <18.5 group showed an increased risk of small-for-gestational age infants. CONCLUSIONS: For women of childbearing age in Beijing, China, the optimal pre-pregnancy BMI range was >=18.5-22.9 kg/m2, with the cutoff value for overweight status being >=23.0 kg/m2 and the cutoff value for obesity being >=28.0 kg/m2.

Associations of polymorphisms of CYP2D6 and CYP2C9 with early onset severe pre-eclampsia and response to labetalol therapy.

PURPOSE: Early onset preeclampsia (PPE) contributes to life-threatening maternal complications and fetal demise. Pharmacogenomics is a precision medicine, and metabolizing enzymes responsive to antihypertensive remains understudied. The aim of this study was to evaluate the associations of polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with PPE and the relationship among CYP2D6, CYP2C9 polymorphisms and response to labetalol therapy. METHODS: Totally 105 gravidas diagnosed with PPE (case) and 103 healthy gravidas (control) were recruited between August 2013 and July 2016. Labetalol was given to control blood pressures (BP) with PPE. If labetalol administration alone did not exceed the mean dose and effectively controlled the BP, it would be considered to be valid (n = 75). Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686, and rs3892097) were analyzed by TaqMan PCR. Differences in the genotype and allele frequencies were compared between case-control groups, and the responsive and nonresponsive to labetalol in PPE. RESULTS: Out of six variants, only CC and CT genotypes of the CYP2D6 variants (rs28371725) in PPE were significantly higher than those in the control group [18.1% (19/105) vs 14.6% (15/103); 56.2% (59/105) vs 42.7% (44/103); χ2 = 6.707]. However, there were no differences in maternal age, diastolic pressure, BMI, BW, serum triglyceride, and creatinine were observed among women with CC, CT, or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P > 0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5 ± 2.1) vs (29.5 ± 1.8) and (29.8 ± 2.2) weeks] and higher plasma albumin [(27.2 ± 9.3) vs (20.3 ± 10.4) and (22.5 ± 7.4) g/L], but lower systolic pressure and 24 h urine protein (LSD test, all P < 0.05). The G allele frequency in CYP2D6 gene rs1065852 nonresponsive to labetalol group was higher than that in responsive labetalol group [93.3% (56/60) vs 76.0% (114/150), χ2 = 8.351, P = 0.004]. CONCLUSIONS: The polymorphism of CYP2D6 gene rs28371725 may be associated with PPE, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of PPE.

The Synthesis and Evaluation of Arctigenin Amino Acid Ester Derivatives.

The use of arctigenin (ARG), a traditional medicine with many pharmacological activities, has been restricted due to its poor solubility in water. Five amino acid derivatives of ARG have been synthesized using glycine, o-alanine, valine, leucine, and isoleucine, which have t-butyloxy carbonyl (BOC) as a protective group. In this study, we examined the effects of removing these protective groups. The results showed that the amino acid derivatives have better solubility and nitrite-clearing ability than ARG. Among the compounds tested, the amino acid derivatives without protective group were the best. Based on these results, ARG and its two amino acid derivatives without protective group (ARG8, ARG10) were selected to evaluate their anti-tumor activity in vivo at a dosage of 40 mg/kg. The results indicated that ARG8 and ARG10 both exhibit more anti-tumor activity than ARG in H22 tumor-bearing mice. The tumor inhibition rates of ARG8 and ARG10 were 69.27 and 43.58%, which was much higher than ARG. Furthermore, the mice treated with these compounds exhibited less damage to the liver, kidney and immune organs compared with the positive group. Furthermore, ARG8 and ARG10 improved the serum cytokine levels significantly compared to ARG. In brief, this study provides a method to improve the water solubility of drugs, and we also provide a reference basis for new drug development.

Emerging tobacco-related cancer risks in China: A nationwide, prospective study of 0.5 million adults.

BACKGROUND: In China, cigarette consumption has increased substantially since the 1980s, almost exclusively in men. This study was aimed at assessing the emerging cancer risks. METHODS: A nationwide, prospective study recruited 210,259 men and 302,632 women aged 30 to 79 years from 10 areas of China from 2004 to 2008; approximately 18,000 incident cancers were recorded during 7 years of follow-up. Cox regression yielded adjusted risk ratios (RRs) comparing smokers (including those who had stopped because of illness but not those who had stopped by choice) with never-smokers. RESULTS: Among men, 68% were smokers; their overall cancer risk was significantly increased (RR, 1.44; 95% confidence interval [CI], 1.37-1.53), and it was greater in urban (RR, 1.55; 95% CI, 1.41-1.70) than in rural areas (RR, 1.39; 95% CI, 1.30-1.49). This excess accounted for 23% of all cancers between the ages of 40 and 79 years, with significantly elevated risks of lung cancer (RR, 2.51; 95% CI, 2.18-2.90), liver cancer (RR, 1.32; 95% CI, 1.12-1.54), stomach cancer (RR, 1.34; 95% CI, 1.16-1.55), esophageal cancer (RR, 1.47; 95% CI, 1.24-1.73), and an aggregate of 5 other minor sites (RR, 1.52; 95% CI, 1.25-1.86). For lung cancer, the RRs were much greater for nonadenocarcinoma (RR, 5.83; 95% CI, 5.02-6.77) than for adenocarcinoma (RR, 1.78; 95% CI, 1.36-2.34). Among exsmokers (6.7%) who had stopped by choice, there was little excess cancer risk approximately 15 years after quitting. Among the few female smokers (3%), the overall cancer risk was also significantly increased (RR, 1.42; 95% CI, 1.28-1.57). Smoking was estimated to cause approximately 435,000 new cancers per year in China (approximately 360,000 in men and approximately 75,000 in women). CONCLUSIONS: In China, smoking now causes a quarter of all adult male cancers. High male uptake rates before the age of 20 years and nearly universal use of cigarettes foreshadow substantial tobacco-attributed risks in China unless there is widespread cessation.

Clinical value of cold knife conization as conservative management in patients with microinvasive cervical squamous cell cancer (stage IA1).

OBJECTIVE: The aim of the study is to evaluate the clinical value of cold knife conization (CKC) as a conservative management in patients with microinvasive cervical squamous cell cancer (SCC). METHODS: This retrospective study enrolled 108 women with diagnosis of microinvasive cervical SCC (stage IA1) by pathology between 2009 to 2012 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Eighty-three patients underwent further hysterectomy. RESULTS: Of the 83 patients (76.9%) who underwent further hysterectomy, 48 patients (57.8%) underwent extrafascial hysterectomy, 30 patients (36.1%) underwent extensive hysterectomy, and 5 patients (6.1%) underwent radical hysterectomy. A total of 19 patients underwent pelvic lymph node dissection without any lymph node metastasis, and a total of 5 patients (4.6%) had lymph vascular space invasion without any positive pelvic lymph node dissection. Of the 83 patients who underwent further hysterectomy and were followed up for 1 year, 18 patients with positive resection margins indicating cervical residual lesions (CIN1-3) have greater likelihood than 65 patients with clear resection margins, but there were no significant differences (P = 0.917); of the 25 patients who underwent CKC as final therapy and were followed up for 1 year, 2 patients with positive resection margins had the second CKC surgery, 1 was diagnosed with CIN1, and the other was diagnosed with cervicitis by pathology; 23 patients had clear resection margins, 2 patients underwent the second CKC 3 months after the first CKC because of the abnormal Thinprep Cytologic Test (TCT) result, and they were both diagnosed with microinvasive cervical SCC (stage IA1) by pathology with clear resection margins. No one enrolled in this study presented metastasis and progression within 1 year of follow-up. CONCLUSIONS: These findings provide the clinical evidences for the possibility of fertility-sparing treatments, especially CKC as conservative treatment for microinvasive cervical SCC. Appropriate further treatments (the second CKC) and follow-up are recommended for patients who strongly desire fertility sparing.

Therapeutic effect of laser vaporization for vaginal intraepithelial neoplasia following hysterectomy due to premalignant and malignant lesions.

AIM: The aim of this study was to evaluate the therapeutic effect of laser vaporization for vaginal intraepithelial neoplasia (VAIN) after hysterectomy in Chinese women and to identify factors affecting persistence/recurrence. MATERIAL AND METHODS: Twenty-eight VAIN patients after hysterectomy due to cervical intraepithelial neoplasia (group 1) and 11 VAIN patients due to cervical cancer (group 2) were reviewed retrospectively. All patients were treated with at least one episode of laser vaporization between 2010 and 2011, and then followed up every 3 months for at least 1 year. Cox regression analysis was used to identify independent factors predicting persistence/recurrence. RESULTS: All VAIN patients achieved remission after two episodes of laser treatment, with 85.7% complete regression in group 1 and 54.5% in group 2. The first episode of the treatment had a significantly higher success rate in group 1 than in group 2 (46.2% vs 0.0%). All patients had no recurrence during a mean follow-up time of 22.8-27.8 months (range 12-39 months). However, infection persisted in 21 (61.8%) of 34 human-papillomavirus-positive patients after laser vaporization. Severity of VAIN was the only significant independent predictor of persistence/recurrence after one episode of the treatment (adjusted odds ratio, 4.08; 95% confidence interval, 1.28-12.96; P = 0.017). Laser treatments were well tolerated with no major side-effects. CONCLUSION: Laser vaporization may be a useful option for the treatment of VAIN after hysterectomy. However, a follow-up is required to assess the long-term efficacy of laser treatment.

Clinical management of cervical intraepithelial neoplasia in pregnant and postpartum women.

OBJECTIVE: To evaluate the clinical management of cervical intraepithelial neoplasia (CIN) and cervical microinvasive squamous cell carcinoma in pregnant and postpartum women. METHODS: This prospective study enrolled 27,230 pregnant women undergoing routine gestational examinations between August 1, 2007 and July 31, 2010 in the Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Colposcopy and cervical biopsy were performed for patients with abnormal Thin Prep® Papanicolaou test (TCT) results. Periodic colposcopy was performed every 8-12 weeks and cervical biopsy was performed if progression was suspected. Cervical cold knife conization was recommended to patients diagnosed with CINIII or microinvasive cervical carcinoma 6-12 weeks after delivery. RESULTS: A total of 2,260 patients had abnormal TCT results (8.12 %). Colposcopy and cervical biopsy were performed for 369 patients. Fifteen patients had microinvasive squamous cell carcinoma, 116 patients had cervicitis, and the number of CIN patients with histological grades I, II, and III were 124, 49, and 65, respectively. Tumor progression during pregnancy was found in 253 patients (CINI or above). Prognosis varied depending on the highest grade of pathological diagnosis results during pregnancy or initial pathological diagnosis results performed 6-12 weeks after delivery by cervical biopsy under colposcopy. Treatment and follow-up were carried out according to diagnoses, state of progression, and reversion (if any). CONCLUSION: These findings underline a need for cervical lesion screening for all women during pregnancy, and colposcopy should be performed for pregnant women who have abnormal TCT results. Appropriate treatment and follow-up were recommended according to different diagnosis of CIN.

[Association of adiponectin gene polymorphisms +45T/G with gestational diabetes mellitus and neonate birth weight].

OBJECTIVE: To determine the association of single-nucleotide polymorphisms (SNPs)+45T/G of adiponectin gene with gestational diabetes mellitus (GDM) and neonate birth weight. METHODS: A total of 264 GDM and 272 pregnant women with normal glucose (NG) were enrolled. DNA was successfully extracted from peripheral blood leucocyte samples. And SNPs+45T/G of adiponectin gene were examined. We also analyzed differences in the genotypic distribution and allelic frequencies in SNP+45T/G of adiponectin gene among GDM group with different neonate birth weights. RESULTS: There was no significant difference between two groups with respects to SNP +45T/G polymorphisms of adiponectin gene (P > 0.05). But significant genotypic difference existed in SNP+45T/G among three GDM groups with different birth weights. Frequencies of T allele were significantly higher in the GDM group with higher birth weight, 68.75% in GDM group with macrosomia and 72.86% in GDM group with 3000-4000 g birth weight (both P < 0.01). And there was no significant difference in SNP +45T/G polymorphisms of adiponectin gene between GDM women and NG group with macrosomia. CONCLUSION: SNP +45T/G polymorphisms of adiponectin gene are not associated with GDM. However, SNP+45T/G polymorphisms of adiponectin gene of GDM women are closely associated with neonate birth weigh. The G/T polymorphisms of SNP+45 of adiponectin are not obviously associated with a higher occurrence of macrosomia in GDM women.

[Expression and function of chemokine TARC/CCR4 at fetal-maternal interface in first trimester].

OBJECTIVE: To investigate the expression and function of thymus and activation regulated chemokine (TARC) and its special receptor CCR4 at placenta villous in the first trimester placenta villous. METHODS: Placenta villous was collected from healthy women undergoing artificial abortion at 6 to 8 weeks of gestation. mRNA levels of TARC, CCR4 were analyzed using semi-quantitative reverse transcription (RT)-PCR methods. Immunohistochemistry assay was used to assess the protein localization and expression of TARC, CCR4. Additionally, extravillous cytotrophoblasts were isolated and cultured. Expression of TARC and CCR4 was measured by immunofluorescence assay. Invasion of cell line HTR8/SVneo was analyzed by transwell assay at concentration of 10, 25, 50 and 100 ng/ml of TARC matched with RPMI 1640 fetal bovine serum free culture medium as control group. In the mean time, blocking experiment was also added to detect TARC regulating cell invasion, which were classified into four groups: control, 100 ng/ml rhTARC, 20 µg/ml anti-TARC+100 ng/ml rhTARC, 100 ng/ml rhTARC+20 µg/ml IgG. The influence of 100 ng/ml TARC on expression level of integrin-α5 and integrin-ß1 were measured by using western-blot assay. RESULTS: (1) In vivo assay:expression of TARC and CCR4 mRNA were detectable in first trimester placenta villous, TARC protein was localized in cytotrophoblasts, syncytiotrophoblasts and cell column especially on the distal portion, while CCR4 protein was localized on invading interstitial cytotrophobalsts. (2) In vitro assay: a. TARC, CCR4 was also expressed in primary isolated extravillous cytotrophoblasts by immunofluorescence assay; b. Matrigel invasion assay demonstrated that TARC had specific dose dependent stimulatory effects on the cells invading through the matrigel precoated filter, the number of cells migration into the lower chamber were:142±31 at 10 ng/ml group, 161±46 at 25 ng/ml group, 201±30 at 50 ng/ml group, 312±48 at 100 ng/ml group, 117±33 at control group, the significant response observed from 25 ng/ml (P<0.05) and reached a peak effect at 100 ng/ml (P<0.01); c. Blocking experiment demonstrated that when trophoblast invasion was monitored in response to TARC neutralizing antibody (15 µg/ml) together with rhTARC 100 ng/ml. The stimulatory activity of rhTARC was completely overcome, with the cells invasion into the lower chambers were 100 ng/ml rhTARC, 20 µg/ml anti-TARC+100 ng/ml rhTARC, 100 ng/ml rhTARC+20 µg/ml IgG, control: 313±47, 113±41, 287±75 and 128±23, respectively; d. Western-blot assay demonstrated that if cells were treated with 100 ng/ml rhTARC, the expression of integrin-α5 were significantly increased (P<0.01), integrin-ß1 level also increased when compared with control (P<0.05). CONCLUSION: TARC was expressed specifically at human fetal-maternal interface. Trophoblast invasion and migration mainly was regulated by up-regulation integrin-α5 and integrin-ß1, which plays an role in trophoblasts differentiation and placentation.

Mesenchymal Stem Cells Ameliorate DSS-Induced Experimental Colitis by Modulating the Gut Microbiota and MUC-1 Pathway.

Purpose: Mesenchymal stem cells (MSCs) have become novel therapeutic agents for the treatment of inflammatory bowel diseases (IBDs). However, the precise cellular and molecular mechanisms by which MSCs restore intestinal tissue homeostasis and repair the epithelial barrier have not been well elucidated. This study aimed to investigate the therapeutic effects and possible mechanisms of human MSCs in the treatment of experimental colitis. Methods: We performed an integrative transcriptomic, proteomic, untargeted metabolomics, and gut microbiota analyses in a dextran sulfate sodium (DSS)-induced IBD mouse model. The cell viability of IEC-6 cells was determined by Cell Counting Kit-8 (CCK-8) assay. The expression of MUC-1 and ferroptosis-related genes were determined by immunohistochemical staining, Western blot, and real-time quantitative polymerase chain reaction (RT-qPCR). Results: Mice treated with MSCs showed notable amelioration in the severity of DSS-induced colitis, which was associated with reduced levels of proinflammatory cytokines and restoration of the lymphocyte subpopulation balance. Treatment with MSC restored the gut microbiota and altered their metabolites in DSS-induced IBD mice. The 16s rDNA sequencing showed that treatment with MSC modulated the composition of probiotics, including the upregulation of the contents of Firmicutes, Lactobacillus, Blautia, Clostridia, and Helicobacter bacteria in mouse colons. Protein proteomics and transcriptome analyses revealed that pathways related to cell immune responses, including inflammatory cytokines, were suppressed in the MSC group. The ferroptosis-related gene, MUC-1, was significantly upregulated in the MSC-treated group. MUC-1-inhibition experiments indicated that MUC-1 was essential for epithelial cell growth. Through overexpression of MUC-1, it showed that upregulation of SLC7A11 and GPX4, and downregulation of ACSL4 in erastin and RSL3-treated IEC-6 cells, respectively. Conclusion: This study described a mechanism by which treatment with MSCs ameliorated the severity of DSS-induced colitis by modulating the gut microbiota, immune response, and the MUC-1 pathway.

[Effects of activating and inhibiting Wnt/ß-catenin signaling pathway on murine model of eutopic endometrium and endometriosis].

OBJECTIVE: To employ the classical Wnt/ß-catenin signaling pathway interference to explore the effects on the functional changes of eutopic endometrium stromal cells and the differences between endometriosis in a murine model. METHODS: Two out of three mouse groups received an injection of either Wnt/ß-catenin signaling pathway activator or blocker. Later the endometrial tissue samples were obtained to develop endometrial stromal cell cultures for the detection of cell invasion ability via Boyden chamber invasion assay and Western blot (WB). Then the methods of WB and Immunohistochemical staining (IHC) were used to examine the factors of eutopic endometrium. And an endometriosis model was established to investigate the factors of signaling pathway via quantitative polymerase chain reaction (QPCR) and IHC. RESULTS: According to WB test, the level of ß-catenin, GSK-3ß and APC in the activation group were significantly higher than in the inhibition group (P < 0.01). In Boyden chamber invasion assay, the number of cells on membranes in the trial group was significantly higher than the control group [(113 ± 12) vs (64 ± 13)]. The expressions of VEGF and MMP-9 in the endometrial stromal cells culture from Boyden chamber assay analyzed via WB were ranked from highest to lowest respectively as activation group (vs control group was 35.6% and 27.4% higher), control group and inhibition group (vs control group was 12.3% and 30.4% lower). Furthermore, the endometrial E-cadherin and VEGF examined via IHC respectively showed a positive expression in inhibitor group and strong positive expression in activation group. QPCR showed the level of Wnt3, Wnt7, GSK3ß, Lef and E-cadherin in the activation group was higher than those in the inhibition group (P < 0.05). CONCLUSION: The intervention of WNT signaling pathway in vivo cause the changes of eutopic endometrial invasion and adhesion function, and further affect the development of endometriosis. Wnt/ß-catenin signaling pathway may promote the eutopic endometrial cell proliferation and improve the ability of eutopic endometrial implantation, invasion, metastasis and angiogenesis.

[Relationship of cytomegalovirus, Chlamydia pneumoniae and herpes simplex virus type 2 infections with preeclampsia].

OBJECTIVE: To explore the potential relationship of cytomegalovirus (CMV), Chlamydia pneumoniae (CP) and herpes simplex virus type 2 (HSV-2) in inflammation and preeclampsia. METHODS: Fifty-two pregnant women with preeclampsia and 34 with uncomplicated pregnancy in the third trimester were recruited. The exclusions included uterine contractions, multiple pregnancies, rupture of membranes, symptomatic infectious diseases, medical diseases and antibiotics or hormones users. Samples of maternal blood were harvested from two groups. Serum levels of CMV, CP, and HSV-2 IgM and IgG antibodies as well as high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) in preeclampsia and normal pregnancy controls. RESULTS: (1) Recent infections of CMV, CP and HSV-2 were not more common in patients with preeclampsia versus normal pregnancy. The prevalence rates of long-dated CMV, CP and HSV-2 infection were 94.2% (49/52), 53.9% (28/52) and 3.9% (2/52) in preeclampsia group versus 100.0% (34/34), 55.9% (19/34) and 5.9% (2/34) in control group. No significant difference existed between two groups (P > 0.05). (2) Maternal serum concentrations of IL-6 and hs-CRP in patients with preeclampsia were significantly higher than that in normal pregnancy women ((7.2 ± 2.1) ng/L and (6.8 ± 5.6) mg/L vs (6.2 ± 1.8) ng/L and (4.6 ± 3.0) mg/L, both P < 0.05). CONCLUSION: Excessive inflammatory reactions are present in women with preeclampsia. But previous infections, as measured by IgM and IgG antibody seropositivity to CMV, CP and HSV-2, are not correlated with preeclampsia in the third trimester.

[Cervical microinvasive squamous carcinoma during pregnancy: observation and outcome of pregnancy with planned delayed treatment].

OBJECTIVE: To evaluate the maternal and fetal outcomes of planned delay in treatment for cervical microinvasive squamous cancer during pregnancy. METHODS: A prospective study of pregnant women was done from August 1, 2007 to May 31, 2010. Pregnant women who had not been carried out cervical cytological screening within one year were got thin-prep cytology test (TCT) screening at their initial prenatal visit. Patients with abnormal cytological results were performed colposcopic examination and directed biopsy. Women with cervical microinvasive cancer were followed up every 8 to 12 weeks. If lesion progression were suspected, compared with previous image, repeated biopsy directed by colposcopy should be performed. Once worsening invasive cancer was confirmed, the pregnancy should be terminated timely. All patients should be reevaluated 6 to 12 weeks postpartum with repeated colposcopic examination and biopsy. All mothers were performed cold knife conization (CKC) at 6 to 12 weeks postpartum. RESULTS: We totally diagnosed 17 cases cervical microinvasive squamous carcinoma during pregnancy. The positive rate is 6.2/10 000 (17/27 230). After informed consent, 15 pregnant women decided to delay treatment until fetal maturation. The mean gestational age of initial diagnosis was (19.3 ± 5.9) weeks. The women were followed up 2 to 4 times during pregnancy. Only 1 patient was verified lesion progression by directed biopsy at 34 weeks and delivered by cesarean section. The progression rate during pregnancy was 1/15. The mean delivered time was (37.1 ± 1.8) weeks (ranged from 34 to 40 weeks). The mean diagnosis-to-delivery interval was (18.4 ± 5.2) weeks. All patients were delivered by cesarean section and all newborns had good outcomes. Finally we confirmed 1 case with cervical cancer stage Ia2, 11 cases with stage Ia1, 3 cases with cervical intraepithelial neoplasia (CIN) III by pathological diagnosis after CKC during 6 to 12 weeks postpartum. All cases were disease free after follow-up ranged from 22 to 48 months. CONCLUSIONS: It is necessary to perform TCT screening for pregnant women who have not been carried out cervical cytology screening within 1 year. If cervical microinvasive squamous cancer were suspected during pregnancy, in order to achieve fetal maturity it is acceptable for the women who desired pregnancy to delay treatment under closely monitoring until postpartum.

[Clinical study on cervical intraepithelial neoplasia with high-risk HPV infection among pregnant women].

OBJECTIVE: To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk (HR) HPV infection among late pregnant women. METHODS: From Aug. 2007 to Feb. 2010, 168 women at 13 to 32 gestational weeks undergoing prenatal examination in Beijing Obstetrics and Gynecology Hospital went through three stage cervical disease screening, including 21 women with cervicitis and 147 women with CIN (42 women with CIN III, 37 women with CIN II and 68 women with CIN I). Hybrid capture assay version II (HC-II) test was used to measure HR-HPV DNA load, and the logarithmic transtormation (log(10)) was performed. All 168 women were followed up to postpartum 3 - 6 months. HR-HPV infections rates of cervicitis and different CIN, the rate of HR-HPV infection turned naturally negative at postpartum of 3 to 6 months, and HR-HPV load at pregnancy and 3 - 6 months postpartum were observed. RESULTS: (1) HR-HPV infection rate: CIN III, II, I and cervicitis pregnant women's HR-HPV positive infection rates were 98% (41/42), 86% (32/37), 76% (52/68) and 62% (13/21) respectively, which reached statistical difference (P = 0.002). (2) HR-HPV naturally negative: the rate of pregnant women with different levels of CIN who turned HR-HPV naturally negative within 3 - 6 months of postpartum were CIN III 5% (2/41), CINII 47% (15/32), CINI52% (27/52) and cervicitis 10/13, which also reached statistical difference among those four groups (P = 0.000). (3) HR-HPV load: pregnant women with different grade of CIN and cervicitis HR-HPV DNA load were CIN III 2.02 ng/L(1.53, 2.67 ng/L), CINII 1.94 ng/L (0.75, 2.75 ng/L), CINI2.04 ng/L (0.08, 2.95 ng/L) and cervicitis 1.98 ng/L (-0.07, 2.47 ng/L). There was no significantly different HPV load in women with cervicitis and different CIN (P = 0.719). At 3 - 6 months postpartum, HR-HPV load was CIN III 1.55 ng/L (0.90, 2.10 ng/L), which was significantly higher than the amount of CINII 0.09 ng/L (-0.69, 1.74 ng/L), CINI0.48 ng/L (-0.56, 2.2 ng/L) and cervicitis -0.46 ng/L (-0.78, 1.40 ng/L, P = 0.036). CONCLUSIONS: With the increasing of CIN grade, the rate of HR-HPV infection in pregnant women was increased, however, the rate of HR-HPV turning negative naturally at 3 - 6 months postpartum decreased. With different CIN grade during pregnancy, HR-HPV DNA load did not change significantly, but HR-HPV DNA load increased at 3 - 6 months of postpartum. HR-HPV DNA loads with the same grade of CIN and cervicitis during pregnancy higher than that of postpartum among pregnant women.

Genetic polymorphisms of killer cell immunoglobulin-like receptor 3DL2 in preeclampsia.

AIMS: We evaluated if killer cell immunoglobulin-like receptor 3DL2 gene (KIR3DL2) polymorphisms are a key factor in the development of preeclampsia. METHODS: In this case-control study, 105 pregnant women with PE (PE group) were enrolled. Their A52G in exon 3 and C32T in exon 9 polymorphisms of the KIR3DL2 genotypes were determined by polymorphism chain reaction-restriction fragment length polymorphism (PCR-RFLP) from venous blood samples and compared with the corresponding KIR3DL2 genotypes of 103 pregnant women with uncomplicated pregnancies (control group). RESULTS: Carriers of the A allele in exon 3 of KIR3DL2 gene occurred less frequently in PE than in controls [P=0.001; odds ratio (OR)=2.65, range: 1.5-4.7]. No significant difference was found about allelic frequencies of KIR3DL2 gene C32T in exon 9 in women with preeclampsia as compared to controls. A significant difference between the two groups of genotypic frequencies of KIR3DL2 gene A52G in exon 3 and KIR3DL2 gene C32T in exon 9 polymorphisms was found (P=0.003 and P=0.000). There was no significant difference between genotypic or allelic frequencies in women with mild preeclampsia compared to sever preeclampsia. CONCLUSIONS: Our results suggest that carriers of A allele in exon 3 have a decreased susceptibility to PE. It is likely that the presence of the CC genotype in exon 9 has a considerable effect on disease progression. The mutation of the two sites is not associated with the severity of preeclampsia.

[Culture and identification of fibroblast from human endometriosis].

OBJECTIVE: To establish the model of cultivating and identifying fibroblast from human endometriosis (HEFC) in vitro. METHODS: The tissues of human endometriotic cysts of ovary were digested by collagenases I, II and IV The resulting cells were purified by centrifugation and differential adhesion. HEFC was identified by observing the morphologic changes under an inverted microscope and the expressions of vimentin, α-SMA (α-smooth muscle actin) and keratin were detected by immunocytochemistry. RESULTS: Immunohistochemical staining of vimentin was positive, α-SMA rarely positive and keratin completely negative in cultured fibroblasts. HEFC grew as a confluent monolayer of short fat fusiform, triangular, star-shaped and polygonal fiber-like cells. Furthermore HEFC could be well sub-cultured. CONCLUSION: Acquired fibroblast can be cultured in vitro stably. It is quite important to study the specificities of HEFC. Sufficient and reliable target cells may be obtained for studying the mechanisms of fibrosis and adhesion in endometriosis at the molecular level.

[Present epidemiological status and clinical characteristics of cervical cancer in Beijing: a report of 1399 patients].

OBJECTIVE: To analyze the prevalence and clinical characteristics of hospitalized patients with cervical cancer over the last two decades in Beijing so as to provide scientific rationales for the management of cervical cancer. METHODS: Stratified cluster sampling was employed to analyze a total of 1399 invasive cervical cancer cases from different class hospitals in Beijing during the period of 1990 - 2009. RESULTS: (1) The number of cervical cancer cases had been rising over the last 2 decades. (2) The age of onset ranged from 17 to 88 years old; the number of patients with stages I, II, III and IV was 772 (57.1%), 380 (28.1%), 182 (13.5%) and 18 (1.3%) respectively; 1135 (83.1%) patients were of squamous cell carcinoma while 182 (13.3%) adenocarcinoma. The last two decades was divided into 4 groups of 5 years each. The average age gradually decreased from 58.2 to 46.0 years old (P < 0.01). The proportion of patients with stages I and II also increased from 69.6% (16/23) to 89.4% (530/856); There was no significant change in histopathologic type of cervical cancer. And squamous cell carcinoma of cervix remained the predominant type (P > 0.05). (3) About 26.0% (364/1399) of cases received no vagino-recto-abdominal examination while 3.4% (48/1399) of cases were not staged. CONCLUSION: Over the last two decades, the number of newly diagnosed cervical cancer cases has showed a rising trend in Beijing. And the proportions of young patients and patients with early disease have both increased. Some irregularities still exist in the diagnosis of cervical cancer. So we should pay more attention to the screening program and standardize the diagnosis, therapy and follow-up of cervical cancer.