[A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis].

Objective: Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate. Methods: This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group (n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group (n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient's satisfaction and side effects were recorded. Results: At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference (P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group (P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups (χ2=1.070, P=0.586). Conclusions: In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

[Efficacy and safety of low-dose levonorgestrel-releasing intrauterine system in Chinese women: a multicenter, single-arm, open labeled interventional trial].

Objective: To evaluate the efficacy, bleeding profile and safety of low-dose levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women of childbearing age. Methods: A multi-center, open-label, single-arm clinical trial conducted at 16 centres in China enrolled 773 healthy women of childbearing age (mean age 31.6 years old, range 18 to 40 years old) , who demanded contraception, from April 2006 to June 2013. All women placed LNG-IUS 8 for 3 years and then been followed up at 3, 6, 9, 12, 18, 24, 30, 36 months. The efficacy variables including pregnancy rate and expulsion rate were analyzed using life table, while observing adverse events (AE) to evaluate the safety. The bleeding profile happened during the study was assessed using 90-day reference intervals (World Health Organization criteria) . Results: Eight pregnancies occurred among 773 women, resulting in a overall Pearl index of 0.42 per 100 women years. The 3-year cumulative pregnancy rate was 0.37 per 100 women years and the 3-year cumulative expulsion rate was 1.99 per 100 women years. The number of women with bleeding/spotting reduced and the bleeding/spotting days declined over time. Totally 219 AE were reported related to LNG-IUS 8 placements. The most common AE were vaginal bleeding (8.2%, 63/773) and the ovarian cyst (6.2%, 52/773) . LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage of women with dysmenorrhea as well as the days of dysmenorrhea decreased over time. The percentage of women satisfied or very satisfied with LNG-IUS 8 was 87.2% (622/713) . Conclusion: LNG-IUS 8 is highly effective and safe for Chinese healthy women of childbearing age.

Scoring system to predict the success rate of external cephalic versions and determine the timing of the procedure.

OBJECTIVE: We aimed to examine the prenatal clinical characteristics of women with single pregnancies undergoing external cephalic version (ECV) without anesthesia, develop a novel scoring system for predicting the ECV success rate, and demonstrate that this scoring system can be used to individualize the timing of ECV attempts. PATIENTS AND METHODS: We enrolled 270 women who underwent ECV without anesthesia at 37-40 weeks of gestation in the Fujian Maternity and Child Health Hospital from 2016 to 2019 and divided them into two ECV outcome groups (success vs. failure). We identified five clinical features (the fetal buttocks' station, the sum of the fundal height and station, the fetal head location, and whether the fetal head or buttocks could be grasped) as independent factors affecting the ECV success rate, and we scored them using a regression coefficient. RESULTS: Women with scores of 0-3 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 16.67%, 16.67%, and 38.88 weeks, respectively; those with scores of 4-6 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 65.75%, 58.90%, and 39.62 weeks, respectively; and those with scores of 7-9 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 93.71%,74.83%, and 40.00 weeks, respectively. CONCLUSIONS: The ECV success and vaginal delivery rates increased with the score, and the delivery gestational age showed an initial increase. To optimize the ECV procedure and reduce the hospital burden, this scoring system should be used routinely to predict the ECV success rate and determine the timing of ECV attempts.

Antifungal susceptibility and genotypes of Candida albicans strains from patients with vulvovaginal candidiasis.

Studies of the genetic diversity of Candida albicans strains and the correlation between the antifungal susceptibility and gene diversity of C. albicans were carried out and the results were found to be inconsistent. To investigate antifungal susceptibility and genotypes of C. albicans strains from patients with vulvovaginal candidiasis (VVC), the genotypes of C. albicans in patients with VVC were studied using a recently developed polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of CAI microsatellite method and antifungal susceptibility was tested using E-test methods. Twenty-six genotypes were identified from 89 strains of C. albicans isolated from patients with VVC. Candida albicans isolates were susceptible to amphotericin B, flucytosine, ketoconazole and fluconazole. The dominant genotypes (A, B, C, D) account for 69.7% (62/89) of C. albicans. The resistant rate of C. albicans genotype B to itraconazole (ITR) and that of C. albicans non-genotype B strains were 66.7% (14/21) and 4.4% (3/68) respectively at P < 0.05. We concluded that C. albicans genotype B from patients with VVC was more resistant to ITR.

SHH expression in placental tissues and trophoblast cell oxidative stress injury during preeclampsia.

OBJECTIVE: To assess the association between Sonic hedgehog (SHH) protein expression levels on placental tissues and the presence of preeclampsia and to assess oxidative stress in cultured trophoblast cells from placentas of women with preeclampsia treated under different conditions. PATIENTS AND METHODS: We enrolled 30 pregnant women with early-onset preeclampsia (<34 weeks), 30 with late-onset preeclampsia (≥34 weeks), and 60 healthy pregnant women with early or late gestational ages for two control groups. We used ELISA tests to measure individual serum SHH levels. Also, we used real-time PCR, and Western blotting to detect Shh transcript and protein levels in placental tissues, respectively, and immunohistochemistry to localize the protein in placental tissues. We isolated trophoblast cells from placentas and cultured them in vitro under different conditions to compare oxidative stress injury and apoptosis rates between them. RESULTS: The mean serum SHH levels in early and late preeclampsia groups were similar (p>0.05). Placentas of women with and without preeclampsia both expressed SHH protein mainly in syncytiotrophoblast cytoplasms. The mean placental SHH protein expressions in both women with early-onset and late-onset preeclampsia were significantly higher than that in the women of the late gestational age control group (p<0.05). The mean Shh mRNA abundances in early-onset and late-onset preeclampsia placentas were significantly higher than that in the late gestational age control placentas (p<0.05). The placental mitochondria oxidative stress injury was significantly higher in the preeclampsia than in the control group (p<0.05). The oxidative stress injury and apoptosis of trophoblast cells were higher in preeclampsia groups than in the late gestational age control group (p<0.05). Trophoblast cells treated with SHH serum had significantly lower oxidative stress than the same cells grown in the presence of preeclamptic serum (p<0.05). CONCLUSIONS: The expression of Shh in placental tissues is associated with the oxidative stress mechanism during preeclampsia.

Genotype distribution of Candida albicans strains associated with different conditions of vulvovaginal candidiasis, as revealed by microsatellite typing.

OBJECTIVE: To compare genotypes of Candida albicans strains causing different conditions of vulvovaginal candidiasis (VVC) in Chinese women. METHODS: C albicans strains were isolated from the vaginas of patients with different conditions of VVC. The genotypes of the strains were investigated based on single-strand conformation polymorphisms (SSCP) of the PCR amplified microsatellite locus CAI. RESULTS: A total of 93 independent C albicans strains was isolated from patients with mild-to-moderate (n = 37) or severe (n = 56) VVC. Thirty of the patients enrolled suffered recurrent VVC. Twenty-six distinct genotypes tentatively designated as A to Z were identified from the 93 C albicans strains compared on the basis of their CAI SSCP patterns. The majority (72.0%) of the strains possessed genotypes A to D, which were similar in the CAI SSCP profiles and were designated as the dominant genotypes. The overall frequencies of the four dominant genotypes were 87.5% (49/56) and 48.6% (18/37; p<0.001) in the C albicans strains from patients with severe and mild-to-moderate VVC, respectively. The strains with the dominant genotypes occupied 83.3% (25/30) and 66.7% (42/63; p = 0.094) in the C albicans strains from patients with recurrent VVC and sporadic VVC, respectively. CONCLUSION: The frequency of C albicans strains with the dominant genotypes (A to D) from patients with severe VVC was significantly higher than that from patients with mild-to-moderate VVC, implying that the CAI genotype distribution of C albicans strains correlates with the severity of VVC.

Human defensins and cytokines in vaginal lavage fluid of women with bacterial vaginosis.

OBJECTIVE: To measure the concentrations of interferon gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, human beta-defensin 2 (HBD-2), and human defensin 5 (HD-5) in the vaginal lavage fluid (VLF) of healthy women and women with bacterial vaginosis (BV). METHODS: VLF samples were obtained from 73 women with BV, 15 women with intermediate vaginal flora, 33 healthy women with vaginal pH greater than or equal to 4.5, and a control group of 39 healthy women with vaginal pH less than 4.5. The concentrations of IFN-gamma, IL-2, IL-4, IL-5, HBD-2, and HD-5 were measured using enzyme-linked immunosorbent assay kits. RESULTS: Concentrations of HBD-2 and HD-5 in the VLF of women with BV were significantly higher than in the control group (P<0.05). IL-4 concentration was significantly lower in the VLF of women with BV than in the control group (P<0.05). CONCLUSIONS: HBD-2 and HD-5 may be involved in defending against invasion by BV-related microorganisms and the decrease in IL-4 concentration may increase susceptibility to BV.

Vaginal allergic response in women with vulvovaginal candidiasis.

OBJECTIVE: To determine the concentration of certain cytokines and immunoglobulin (Ig) E in the vaginal lavage fluid (VLF) of women with vulvovaginal candidiasis (VVC). METHOD: Cytokin and IgE concentrations were measured in the VLF of women with VVC; women free of any genital infections acted as controls. RESULT: The VLF concentrations of interleukin (IL)-2, IL-8, and interferon (INF)-gamma were higher among women with VVC than in the control group; women with severe VVC had a higher VLF concentration of IL-4 than those with mild to moderate VVC; women with cured VVC had a higher VLF concentration of IL-13 than did controls; and women with VVC or cured VVC had a higher VLF concentration of IgE than did controls (P<0.05 for all). CONCLUSION: Both helper T cells type 1 and innate response cytokines were shown to play a dominant role in the pathogenesis of VVC. This allergic vaginal response in women with VVC suggests that the form of treatment for VVC should be reconsidered.

Serum proteomic features for detection of endometrial cancer.

To find new potential biomarkers for detection of endometrial cancer (EC), 70 serum samples including 40 from EC patients and 30 from normal healthy females were detected by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) using WCX2 (weak cation exchange) protein chip. Mass spectra were then assessed with three powerful data-mining tools: a tree classifier, Biomarker Wizard software, and Biomarker Patterns System. The diagnostic pattern combined with 13 potential biomarkers could differentiate EC patients from healthy persons, with a specificity of 100%, sensitivity of 92.5%, and total coincidence of 95.7%. The combination of surface-enhanced laser desorption-ionization with bioinformatics tools could help find new biomarkers and establish with high sensitivity and specificity for the detection of EC.

Regulation of vascular adaptation during pregnancy and post-partum: effects of nitric oxide inhibition and steroid hormones.

Treatment of pregnant rats with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), has been shown to produce symptoms similar to pre-eclampsia (i.e. elevated blood pressure, proteinuria and fetal growth retardation). After L-NAME infusion is initiated on day 17 or 18 of gestation, the blood pressure proceeds in a biphasic pattern (immediate rise, followed by a decline, then increasing again in the post-partum period). The blood pressure actually begins to rise prior to delivery on days 21-22, i.e. after progesterone withdrawal occurs, suggesting that these responses may be regulated by changes in steroid hormone concentrations during pregnancy. Therefore, we evaluated the effects of the different steroid hormones: progestins (progesterone, promegestone, levonorgestrel), antiprogestins (mifepristone), 17 beta-oestradiol or androgens (testosterone, dihydrotestosterone) on systolic blood pressure in pregnant, non-pregnant female and normal male rats with and without L-NAME treatment and spontaneously hypertensive male rats. The animals received continuous infusions of L-NAME (150 mg/kg/day) or vehicle through osmotic mini-pumps and daily s.c. injections of steroid hormones. In pregnant rats the pump was inserted on day 17 or 18 of gestation and steroid hormone injections were started on the first day following delivery at term and continued daily until post-partum day 10. In non-pregnant female or male rats steroid hormone injections were initiated 5 days after the L-NAME pump was inserted. Systolic blood pressure was measured daily from the tail with a pneumatic tail-cuff device. R5020 (1.5 mg/kg/day) significantly attenuated the blood pressure elevation induced by L-NAME during the post-partum period. Similarly, it lowered blood pressure in L-NAME treated non-pregnant female rats or male rats. R5020 also lowered blood pressure in spontaneously hypertensive male rats. Progesterone (6 mg/kg/day) had similar effects on blood pressure in the post-partum period, although it also lowered the blood pressure in control animals. Interestingly, administration of two different doses of levonorgestrel (0.3 and 1.5 mg/kg/day) did not decrease the blood pressure in either L-NAME-infused rats or controls. Mifepristone (RU486, 30 mg/kg/day) further increased blood pressure in L-NAME-treated rats post-partum. 17 beta-oestradiol (30 micrograms/kg/day) had no effect on blood pressure in either L-NAME infused rats in the post-partum period or controls, whereas both testosterone (0.3 mg/kg/day) and dihydrotestosterone (0.3 mg/kg/day) significantly attenuated the blood pressure increase after L-NAME, while raising the blood pressure in vehicle-infused animals. These results suggest that the control of systemic blood pressure during pregnancy may be modulated by steroid hormones. Progesterone may be the steroid hormone with the major action on vascular tension during pregnancy.

The effect of indomethacin and prostacyclin agonists on blood pressure in a rat model of preeclampsia.

OBJECTIVE: This study was designed to determine the effects of cyclooxygenase inhibition and prostacyclin agonists on the hypertension induced by nitric oxide synthase blockade in a previously characterized rat model of preeclampsia. STUDY DESIGN: A condition similar to preeclampsia was induced by infusing pregnant rats with the nitric oxide synthase inhibitor N G -nitro- L -arginine methyl ester through subcutaneously implanted osmotic minipumps. Blood pressure was measured with the tail cuff method. In the first experiment the rats received either vehicle alone (control group), N G -nitro- L -arginine methyl ester (50 mg/d), indomethacin (0.1 mg/d), or N G -nitro- L -arginine methyl ester plus indomethacin beginning on day 17 of pregnancy. In the second experiment the rats received vehicle alone (control group), N G -nitro- L -arginine methyl ester (50 mg/d), or N G -nitro- L -arginine methyl ester plus iloprost (31 microgram/d). In a third experiment cicaprost (15 microgram/d) was substituted for iloprost. RESULTS: Except for an increase on the day after insertion of the pump indomethacin had no significant effect on the hypertension induced by N G -nitro- L -arginine methyl ester. Both prostacyclin agonists (iloprost and cicaprost), however, attenuated the rise in blood pressure usually seen after N G -nitro- L -arginine methyl ester administration. CONCLUSIONS: Nonselective inhibition of the cyclooxygenase enzymatic system does not influence the hypertension seen in the rat preeclampsia model induced by chronic nitric oxide deficiency. The hypertension in this model can be partially reversed with prostacyclin analogs.

Effect of chronic treatment with 17beta-estradiol and progesterone on endothelium-dependent and endothelium-independent relaxation in isolated aortic rings from ovariectomized rats.

OBJECTIVE: Our purpose was to study the influence of chronic treatment with sex hormones on endothelium-dependent and endothelium-independent relaxation of rat aortic rings. STUDY DESIGN: Rings of aortas, with and without endothelium, from rats treated with sex hormones or vehicle for 10 days were mounted in organ baths for isometric tension recording. Indomethacin (10(-5) mol/L) and N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), alone or in combination, were used to block cyclooxygenase and nitric oxide synthase, respectively. Mean data of contraction induced by potassium chloride (60 mmol/L), the relaxation by acetylcholine (10(-6) mol/L) in potassium chloride-contracted rings, tension induced by phenylephrine, and the negative logarithm of the concentration of acetylcholine or 3-morpholinosydnonimine producing a 50% relaxation, and area under the curve were calculated. RESULTS: Treatment with 17beta-estradiol (10 microg/rat/day) decreased the tension induced by 60 mmol/L potassium chloride and increased the relaxation by acetylcholine in the rings with endothelium precontracted with potassium chloride. Contraction induced by potassium chloride and relaxation induced by acetylcholine were not influenced by the treatment with progesterone (2 mg/rat/day) or estrogen-progesterone combination. Treatment with estradiol, progesterone, or both hormones had no effect on tension developed in intact rings in response to phenylephrine and did not influence endothelium-dependent relaxation to acetylcholine or endothelium-independent relaxation to 3-morpholinosydnonimine in rings contracted with phenylephrine. The inhibition by N(omega)-nitro-L-arginine methyl ester of endothelium-dependent relaxation by acetylcholine was attenuated after the treatment with the sex hormones. CONCLUSIONS: Chronic treatment with sex hormones did not increase production or release of endothelium-derived relaxing factor and did not change the sensitivity of rat aortic smooth muscle to nitric oxide. The treatment slightly counteracted the inhibition of endothelium-dependent relaxation produced by nitric oxide synthase blocker.