Gender differences in UV-induced skin inflammation, skin carcinogenesis and systemic damage.

Ultraviolet (UV) radiation-induced chronic inflammation contributes to all stages of skin tumor development. In addition, gender plays an important role in inflammatory diseases or cancer. In this study, histopathology changes, hematology, oxidative stress and inflammatory response were used to evaluate sex differences in UV-induced chronic inflammation-associated cancer development. The results showed that the male and female mice had photoaging damage at the 9th week. However, skin tumors only appeared in male mice at 31st week. Furthermore, UV increased ROS production, p65, p-p65, IL-6 and TNF-α protein expressions in skin, and these factors elevated more in male mouse model. Hematology results showed that the parameters of blood systemic inflammation were changed in different degrees in model groups, while the pathological results showed inflammatory cell infiltration in the internal organs of both model groups in varying degrees. These results indicate that there are gender differences in UV-induced skin inflammation, carcinogenesis and systemic damage. Moreover, male mice are more sensitive to UV irradiation, which may be responsible to greater oxidative stress and inflammatory damage.

Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects.

Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g(-1). The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the theranostic treatment of CNS diseases.

Dual-color labeled anti-mucin 1 antibody for imaging of ovarian cancer: A preliminary animal study.

To investigate the feasibility of the anti-mucin 1 (anti-MUC1/CD227) antibody in the fluorescent imaging of ovarian cancer, the CD227 antibody and a control IgG antibody were labeled with a near-infrared dye [Cy5.5-N-hydroxysuccinimide (NHS)] and a green dye (fluorescein-NHS). In vivo fluorescence images were obtained at 4, 12 and 36 h after injection of the probes into OVCAR3 tumor-bearing mice. The tumor to background ratios were calculated for both probes. Ex vivo fluorescence images were obtained following sacrifice at 36 h. After conjugation to Cy5.5 and fluorescein, the dual-color labeled CD227 probe (Ab-FL-Cy5.5) could be visualized by both green and near-infrared fluorescence. Uptake by the tumors was higher for the Ab-FL-Cy5.5 than for the IgG-Cy5.5 probe. All tumors could be visualized by in vivo imaging with an acceptable tumor to background ratio. Ex vivo studies demonstrated the advantages of using green fluorescence imaging to guide the resection of tumor tissues. These preliminary data indicate that the Ab-FL-Cy5.5 probe is promising for further tumor imaging applications and clinical translation.

Fasting plasma glucose at 24-28 weeks to screen for gestational diabetes mellitus: new evidence from China.

OBJECTIVE: To evaluate the usefulness of a fasting plasma glucose (FPG) at 24-28 weeks' gestation to screen for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined. RESULTS: FPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928. CONCLUSIONS: FPG at 24-28 weeks' gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.

[Effect of lipoxin A(4) on lipopolysaccharide-induced endothelial hyperpermeability in human umbilical vein endothelial cell].

OBJECTIVE: To explore whether lipoxin A(4) (LXA(4))could prevent lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVEC) monolayer hyperpermeability and its possible mechanism. METHODS: Human umbilical cords were obtained from women with normal pregnancy immediately after delivery from Tongji Hospital Affiliated of Tongji Medical College. Primary HUVEC were isolated from umbilical veins and subcultured, then, HUVEC were divided into four groups:control group; LPS group (10 mg/L of LPS); LPS + LXA(4) group(10 mg/L of LPS and 100 nmol/L of LXA(4)); LPS + LXA(4) + BOC-2 group [10 µmol/L of BOC-2, an effective antagonist of formyl peptide receptor like 1 (FPRL-1)]. All expriments were performed after cells were treated for 24 hours. Endothelial permeability was measured by fluorescein isothiocyan-ate labelled bovine serum albumin (FITC-BSA) clearance across the monolayer; tumor necrosis factor α (TNF-α) mRNA and secretion were detected by reverse transcriplase (RT)-PCR and ELISA assay respectively, and nuclear factor κB (NF-κB) protein change was determined by western blot. RESULTS: (1) LPS induced a significant increase in the permeability [Pa value of LPS group was (183.1 ± 1.7)%], while co-administrating with LXA(4) obviously attenuated this LPS-induced hyperpermeability, Pa value of LPS + LXA(4) group was (103.1 ± 2.2)%, LPS + LXA(4) + BOC-2 group was (162.2 ± 2.8)%, control group was 100%, the permeability of HUVEC monolayer was significantly increased by LPS which was (83.1 ± 1.7)% of control (P < 0.01), however, it was notably inhibited by LXA(4) (P < 0.05); the blockade of FPRL-1 could attenuate the effect of LXA(4), that is, there was no difference between the LPS + LXA(4) + BOC-2 group and the LPS group. (2) After treatment with different concentration of LPS(0, 0.1, 1, 10 mg/L), the mRNA expressions of TNF-α were increased (1.11 ± 0.11, 1.27 ± 0.03, 1.60 ± 0.06, 1.82 ± 0.04, respectively), compared with the control group, at the concentration of 1, 10 mg/L LPS, the difference was statistically significant (P < 0.05). (3) The increased levels of NF-κB and inflammatory mediator TNF-α in the LPS group were both inhibited by LXA(4). Levels of NF-κB protein and TNF-α mRNA secretion in LPS treated group (0.53 ± 0.06 and 0.81 ± 0.09, respectively) were both inhibited by LXA(4)(0.19 ± 0.05 and 0.41 ± 0.07, respectively, and both had significant difference, P < 0.05). (4) Levels of TNF-α in HUVEC culture medium of LPS group [(31.94 ± 0.01) ng/L] was significantly higher than the control group [(18.17 ± 0.03) ng/L, P < 0.05], LPS + LXA(4) group [(15.72 ± 0.07) ng/L] was significantly lower than the LPS group (P < 0.05). CONCLUSION: Our findings demonstrated that LXA(4) could prevent the endothelial cell hyperpermeability induced by LPS in HUVEC under which the possible mechanism was through inhibiting the expression of NF-κB and its related cytokines through receptor-dependent.

Effects of oral contraceptives and metformin on the outcome of in vitro maturation in infertile women with polycystic ovary syndrome.

UNLABELLED: Abstract Objective: To evaluate the effects of oral contraceptives and metformin on the outcome of in vitro maturation (IVM) in infertile women with polycystic ovary syndrome (PCOS). METHODS: This is a retrospective study of 108 women with PCOS, subject to 152 cycles of IVM treatment. The study was held at the Reproductive Medicine Center of the First Affiliated Hospital of Wenzhou Medical College, People's Republic of China. Before entering IVM treatment, 54 patients who received oral contraceptive pill (marvelon, 0.15 mg desogestrel, and 0.03 mg ethinylestradiol), one tablet every day, and metformin 500 mg twice or three times per day were defined as the pretreated group, and another 64 patients who were not administered any drugs as the control group. The main outcome measures were the rates of oocyte maturation, fertilization, cleavage, miscarriage, clinical pregnancy, and live birth. RESULTS: There were no significant differences between the two groups in the rates of oocyte maturation, fertilization, cleavage, and clinical pregnancy (p > 0.05). A significantly lower miscarriage rate was obtained in the pretreated group than in the control group (16.13% vs 4.0%, p < 0.01). The live birth rate per embryo transfer seemed to be higher in the pretreated group than in the control group (37.70% vs 30.38%, p = 0.363), but was not statistically significant. CONCLUSIONS: Pretreatment with oral contraceptives and metformin improved the outcome of IVM related to the miscarriage rate and possibly also live birth rate.

[Effect of lipoxin A(4) on lipopolysaccharide-induced oxidant stress in human umbilical vein endothelial cells].

OBJECTIVE: To explore the effects of lipoxin A(4) (LXA(4)) on lipopolysaccharide (LPS)-induced oxidative stress in human umbilical veins endothelial cells (HUVEC) and the possible mechanism. METHODS: Neonatal umbilical cords were obtained from normal term pregnant women with cesarean section within 4 hours and then were used to isolate HUVEC for subculture. HUVEC were divided into four groups:control group; LPS group (10 µg/ml of LPS); LPS + LXA(4) group (10 µg/ml of LPS and 100 nmol/L of LXA(4)); LXA(4) group (100 nmol/L of LXA(4)). All expriments were performed after cells treated for 12 and 24 hours respectively. Immunofluorescence was used to detect the expression of VIII foctor and nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2); the mRNA expression of Nrf2, heme oxygenase 1 (HO-1) and reduced form of nicotinamide-adenine dinucleotide quinone oxidoreductase-1 (NQO1) were evaluated by reverse transcription-PCR. RESULTS: (1) The flavovirens fluorescence was observed in the cytoplasm under fluorescence microscope, which confirmed the existence of VIII factor which specifically expressed in endothelial cells, especially in HUVEC. (2) Immunofluorescent results showed that in control group, Nrf2 protein expressed in the cytosol rather than in the nucleus. In LPS group, the expression of Nrf2 protein obviously increased in the nucleus while decreased in the cytosol after 12 hours. However, after LPS treatment for 24 hours, Nrf2 expression reduced in the cytosol and nucleus. In co-treatment with LPS and LXA(4) group, the expression of Nrf2 protein was much higher than that in LPS group after 12 hours or 24 hours. Furthermore, Nrf2 protein also mostly expressed in the cytosol in LXA(4) group. (3) After stimulation for 12 hours, compared with control group, the gene expression of Nrf2 and HO-1 were significantly enhanced in LPS group (0.581 ± 0.019 and 0.081 ± 0.009, P < 0.05) and in LPS + LXA(4) group (0.692 ± 0.048 and 0.136 ± 0.018, P < 0.05), the level of NQO1 mRNA in LPS group and LPS + LXA(4) group were 0.381 ± 0.009 (P > 0.05) and 0.574 ± 0.034 (P < 0.05). After treatment for 24 hours, compared with control goup, the gene expressions of Nrf2 and NQO1 were down-regulated in LPS group (0.180 ± 0.017 and 0.472 ± 0.064, P < 0.05). But in LPS + LXA(4) group the expression of Nrf2 and NQO1 were upregulated (0.532 ± 0.051 and 0.830 ± 0.068, P < 0.05, compared with treatment for LPS group). The mRNA expressions of Nrf2, HO-1 and NQO1 were increased in LPS + LXA(4) group compared with LPS group (P < 0.05). In addition, there was no markedly difference in the expressions of Nrf2, HO-1 and NQO1 between control and LXA(4) group after 12 hours and 24 hours (P > 0.05). CONCLUSION: Through activating nuclear translocation of Nrf2 protein from cytoplasm, LXA(4) upregulates the Nrf2 downstream enzymes, such as NQO1 and HO-1 to protect HUVEC against the oxidative stress induced by LPS.

[Protective effects and its mechanism of lipoxins on human umbilical vein endothelial cells under hypoxia].

OBJECTIVE: To investigate protective effects and mechanisms of lipoxinA(4) (LXA(4)) on human umbilical vein endothelial cells (HUVEC) under hypoxia in vitro. METHODS: The HUVEC culture were divided into groups as followed: added M199 culture medium as normal control groups, added CoCl2 to mimic hypoxia in vitro as hypoxia group and added different concentrations of LXA(4) (1, 10, 100 nmol/L) were added to the induced hypoxial HUVEC as agents intervention group. Morphological changes of HUVEC were observed by using inverted phase contrast microscope. The influence of LXA(4) on cell survival was investigated by methyl thiazolyl tetrazolium (MTT) assaying method after the treatment with different concentrations of LXA(4) and 100 nmol/L lipoxinA(4) according to different time (4, 8, 12 and 24 hours). The expression of von-willebrand factor (vWF) was detected by immunocytochemistry method. The changes of cytosolic Ca(2+) were measured by laser scanning confocal microscope. RESULTS: (1) Morphological changes:the cells under hypoxia lost its normal shapes and showed necrosis, while the cells cocultured with 100 nmol/L LXA(4) were normal appropriately. (2) Survival rate: the survival rates of HUVEC under hypoxia was (40.1 +/- 3.9)% and increased to (52.9 +/- 1.4)%, (64.1 +/- 3.3)%, (76.6 +/- 1.6)% respectively when added with LXA(4) with concentration of 1, 10, 100 nmol/L into culture medium. There was significant different survival rate when compared with that of hypoxia group. (3) The level of vWF: The expression of vWF was decreased with the increasing concentrations of LXA(4) added into culture medium, the gray values were 203.9 +/- 0.7 in 1 nmol/L, 204.6 +/- 0.9 in 10 nmol/L, 191.8 +/- 0.5 in 100 nmol/L respectively, which reached statistical difference in comparison with that of hypoxia groups (P < 0.05). (4) Confocal analysis: the intracellular free Ca(2+) concentrations of HUVEC were intensified with LXA(4) treatment. CONCLUSIONS: LXA(4) plays an important role in keeping the normal shape of HUVEC under hypoxia, can enhance survival of hypoxial HUVEC and decrease the level of vWF in cytoplasm. The protective mechanism might be via decreasing mitochondria Ca(2+) overload and increasing cytoplasm Ca(2+) by nucleus Ca(2+) transference.

[Clinical characteristics of 7 patients with gestational diabetes insipidus].

OBJECTIVE: To investigate the clinical feature, treatment and prognosis of both the mother and the fetus with gestational diabetes insipidus. METHODS: A total of 7 cases of gestational diabetes insipidus collected in the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Combination of Traditional Chinese Medicine with Western Medicine Hospital, and Zhejiang Taizhou Hospital from June 1993 to June 2006 were analyzed retrospectively. RESULTS: Seven cases symptoms all characterized by excessive thirst polydipsia and polyuria. The average 24 h urinary output was between 11 L to 13 L and manifested of hypobaricuria. After effective treatment (three cases were treated with 1-deamino-8-D-arginine vasopressin, another three patients were managed with hydrochlorothiazide, and the last one was cured with antisterone), seven patients with gestational diabetes insipidus did not have any severe consequences. Their symptoms of excessive thirst, polyuria, and polydypsia disappeared from 7 days to 3 months after parturition. Urinary volume returned to normal standard of 1000-2000 ml during 24 hours. Specific gravity of urine recovered normally between a range 1.015-1.025 and serum sodium recovered between 135-147 mmol/L. The average duration of illness was 52 days. Eight newborn infants survived. Two of them were sent to neonatal intensive care unit for treatment. One was because of premature delivery caused by antepartum eclampsia, and the other case was one of the twins who had hydronephrosis. The baby of the first case left hospital after 3 weeks' treatment. The latter one's symptom disappeared 2 weeks after delivery. No obvious symptom was discovered among all the babies through follow-up telephone calls 42 days after childbirth. CONCLUSION: Gestational diabetes insipidus is a rare endocrinopathy complicating pregnancy. This disorder is characterized by excessive thirst, polydypsia, polyuria, hypobaric urine and electrolyte disturbances usually manifesting in the third trimester of pregnancy or puerperium. This is a transient syndrome. The first treatment of choice in patients with gestational diabetes insipidus is 1-deamino-8-D-arginine vasopressin and the second-choice is hydrochlorothiazide. Early diagnosis and appropriate management of the disease may reduce the hazard for both the mother and the fetus during perinatal period.

[Effect of lipoxins on proliferation and secretion of peritoneal macrophages from patients with preeclampsia in vitro].

OBJECTIVE: To study the effect of lipoxins on the proliferation and secretion of peritoneal macrophages from patients with preeclampsia in vitro. METHODS: Peritoneal macrophages were obtained from 24 patients with preeclampsia (preeclampsia group) and 24 normal pregnant women (normal pregnant group) who were treated in the First Affiliated Hospital of Wenzhou Medical College from March to July 2007. Enzyme linked immunosorbent assay (ELISA) was used to detect the concentration of tumor necrosis factor-alpha (TNF-alpha) in the supernatant of macrophages which were pulsed with lipoxins at different concentrations (0, 10, 100 nmol/L) in both groups after 48 hours. Methyl thiazolyl tetrazolium (MMTT) assay was used to detect the inhibition rate of cell proliferation of macrophages which were pulsed with lipoxins at different concentrations (0, 10, 100 nmol/L) in both groups after 24 hours. RESULTS: (1) The concentration of TNF-alpha: the levels of TNF-alpha were (1867.5 +/- 47.3), (1836.9 +/- 4.5) and (1800.5 +/- 2.7) ng/L after treatment with different concentrations of lipoxins (0, 10, 100 nmol/L) in preeclampsia group vs normal pregnant group [(791.3 +/- 62.2), (789.4 +/- 2.3), (781.5 +/- 1.9) ng/L]. The levels of TNF-alpha in preeclampsia group were significantly higher than that in normal pregnant group (P < 0.05). Lipoxins significantly inhibited the concentration of TNF-alpha in a dose-dependent manner in preeclampsia group (P < 0.05), while it had no significant effect in normal pregnant group (P > 0.05). (2) Cell proliferation inhibition: Incubation with lipoxins produced a dose-dependent (0, 10, 100 nmol/L) inhibitory effect on proliferation in preeclampsia group, [ 14. +/-6. )% , (32. +/-3.6)%, ( 6. ++/-3. )% vs normal pregnant group [(16.8 +/- 6.9)%, (16.7 +/- 5.4)%, (15.9 +/- 2.1 )%]. The rate of cell proliferation in preeclampsia group was significantly higher than that in normal pregnant group. Lipoxins significantly inhibited this growth (P < 0.05) , while it had no significant effect in normal pregnant group (P > 0.05). CONCLUSION: Lipoxins can inhibit the proliferation of macrophage and secretion of TNF-alpha in preeclampsia in a dose-dependent manner. Lipoxins may be potentially useful in prevention and treatment of preeclampsia.

Formyl-peptide receptor like 1: a potent mediator of the Ca2+ release-activated Ca2+ current ICRAC.

In electrically non-excitable cells, one major source of Ca(2+) influx is through the store-operated (or Ca(2+) release-activated Ca(2+)) channel by which the process of emptying the intracellular Ca(2+) stores results in the activation of Ca(2+) channels in the plasma membrane. Using both whole-cell patch-clamp and Ca(2+) imaging technique, we describe the electrophysiology mechanism underlying formyl-peptide receptor like 1 (FPRL1) linked to intracellular Ca(2+) mobilization. The FPRL1 agonists induced Ca(2+) release from the endoplasmic reticulum and subsequently evoked I(CRAC)-like currents displaying fast inactivation in K562 erythroleukemia cells which expresses FPRL1, but had almost no effect in K562 cells treated with FPRL1 RNA-interference and HEK293 cells which showed no FPRL1 expression. The currents were impaired after either complete store depletion by the sarco/endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin, or after inhibition of PLC by U73122. Our results present the first evidence that FPRL1 is a potent mediator in the activation of CRAC channels.

[Perinatal outcomes of 45 pregnant women with pulmonary hypertension complicating congenital heart disease].

OBJECTIVE: To explore the perinatal outcomes of women with pulmonary hypertension complicating congenital heart disease (CHD). METHODS: Clinical data of 45 cases of pregnant women with pulmonary hypertension complicating CHD from Apr 1995 to May 2007 were analyzed and they were divided into three groups: 29 cases of slight group [pulmonary hypertension of 30 mm Hg (1 mm Hg = 0.133 kPa) to 49 mm Hg], 8 cases of moderate group (pulmonary hypertension of 50 mm Hg to 79 mm Hg) and 8 cases of severe group (pulmonary hypertension equal to or higher than 80 mm Hg). The types of CHD, cardiac functional status (New York heart association, NYHA), gestational weeks of pregnancy termination, mode of delivery, pregnancy after CHD operation and outcomes of infants were compared between the groups. RESULTS: (1) The highest incidence of CHD were atrial septal defect and ventricular septal defect (58%, 26/45). The rate of pregnant women after CHD operation was 29% (13/45), they were mainly in slight group and their NYHA class were in I - II. (2) The occurrence rate of NYHA class III - IV was 7 /8 in severe group. The rate of NYHA class I - II was 6/8 in moderate group. The rate of NYHA class I - II was 97% (28/29) in slight group. (3) The rate of term delivery was 93% (27/29), preterm labor 3% (1/29), abortion 3% (1/29), and the birth weight was (3153 +/- 399) g on average in slight group. The rate of term delivery was 5/8, preterm labor occurred in 3 cases in moderate group. The rate of term delivery was 5/8, preterm labor occurred in 2 cases, and iatrogenic abortion in 1 case in severe group. The average birth weight between slight group and moderate or severe group had a significant difference. (4) Caesarean section rate was 78% (35/45) among all patients. The rate of cesarean section delivery was 76% (22/29) in slight group, 6/8 in moderate group, and 7/8 in severe group. (5) The rate of pregnant women who had portent heart failure or heart failure was 24% (11/45), overall maternal mortality was 4% (2/45). CONCLUSIONS: The higher the pulmonary hypertension, the worse the outcome of the mother and fetus; The pregnant women with good heart function after cardiac operation would have a good perinatal outcome. Cesarean section is more suitable for those women.

[Expression of FHIT genes in CIN and cervical carcinoma and the relationship between FHIT gene and p53 and HPV16/18].

OBJECTIVE: To investigate the role and significance of FHIT genes depletion, p53 overexpression and HPV16/18 infection in cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC). METHODS: Tumor samples taken from 52 cases of CIN and 69 cases of CC were processed by immunohistochemistry (SP) to determine the expression of FHIT genes and p53 protein, by in situ hybridization to detect HPV16/18 infection, and were compared with those in 18 cases of normal cervical tissues as control. RESULTS: (1) The FHIT expression was positive in normal cervical tissue with no depletion occurred, and was 30.8% in CIN. It was significantly higher in CIN III and carcinoma groups than that in normal and CIN I/II groups (P < 0.01). The depleted expression of FHIT in infiltrating cervical carcinoma group was 66.7% (46/69), significantly higher than that in normal and CIN groups (P < 0.01). Along with the decreasing of cell differentiation, the negative rate of FHIT raised. (2) The positive expression of p53 in CC group was 56.5% (39/69) and the HPV16/18 was 84.1% (58/69), both higher than that in CIN and normal groups (P < 0.05). (3) In CIN and CC groups, the positive rate of p53 in cases with positive or negative FHIT expression was similar (P > 0.05). (4) There is a negative correlation between FHIT and p53 expression. The rate of HPV16/18 infection in the depleted expression of FHIT group was significantly higher than that in FIHT normal expression group (P < 0.01). CONCLUSION: (1) The FHIT-depletion is related with cervical carcinogenesis. It may be used as a marker to serve mass screening of CIN-high risk subjects and diagnostic indicator for early cervical carcinoma. (2) Depleted expression of FHIT is frequently associated with p53 over-expression in CIN and CC subjects, but there is no direct correlation between them. (3) HPV16/18 infection may probably be the common cause leading to altered FHIT and p53 expression.

[Expression of cyclooxygenase-2 mRNA and identification of its spliceriant in human myometrium obtained from women in labor].

OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splice variant of COX-2. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for investigating the expression of COX-2. According to the sequence of rat COX-2 splice variant, the primers were designed and synthesized, then the splice variant of COX-2 in human myometrium from woman in labor was identified, cloned into vector and sequenced. RESULTS: The results showed that (1) The Expression of COX-2 mRNA was lower in human myometrium obtained from women who were not in labor than those in labor. (2) A new band of COX-2 was obtained in myometrium from a woman in labor. The fragment includes an unspliced intron, which locates between exons 7 and 8. CONCLUSION: COX-2 gene is not only expressed highly in human myometrium from women in labor, but also produced splicing variant by alternative splicing.

[Associations between six functional genes and schizophrenia].

OBJECTIVE: To assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1). METHODS: With the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population. RESULTS: (1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05). CONCLUSION: The 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.