[Effects of interpregnancy interval on pregnancy outcomes of subsequent pregnancy: a multicenter retrospective study].

Objective: To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy. Methods: A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO's recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics. Results: A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant (P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% (OR=1.42, 95%CI: 1.07-1.88, P=0.015), 46% (OR=1.46, 95%CI: 1.13-1.88, P=0.004), and 64% (OR=1.64, 95%CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study (P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age (OR=2.87, 95%CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 (OR=1.59, 95%CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes (OR=1.58, 95%CI: 1.18-2.13, P=0.002) and premature delivery (OR=1.52, 95%CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM (OR=5.34, 95%CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM (OR=1.44, 95%CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia (OR=4.11, 95%CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia (OR=1.46, 95%CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery (OR=1.47, 95%CI: 1.13-1.92, P=0.004). Conclusions: Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

[Survey of related factors of maternal venous thromboembolism in nine hospitals of China].

Objective: To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country. Methods: Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it's disease status and risk factors. Results: (1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575). Conclusions: The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.

[Analysis of clinical efficacy, safety and prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer].

Objective: To retrospectively analyze the clinical efficacy, safety and the main factors affecting the prognosis of anlotinib hydrochloride in the treatment of advanced primary liver cancer. Methods: Fifty-five cases with advanced primary liver cancer who received anlotinib hydrochloride were enrolled. The baseline data of the patients, such as prothrombin time, total bilirubin, albumin, Child-Pugh score, procalcitonin, alpha fetoprotein, extrahepatic metastasis, cirrhosis, portal hypertension, whether or not combined surgery, pathological staging, etc before treatment were recorded. Hematological and imaging results of the patients were reviewed. Adverse events that appeared in patients at any time until the end of follow-up or loss- to- follow-up or death were recorded. The survival curve was plotted by Kaplan-Meier method, and the difference of survival time between groups was examined by log-rank test. Cox regression model of single and multiple factor were used to analyze the factors affecting the prognosis. Results: As of the last follow-up, 2 patients were lost-to-follow-up, 30 died, and 23 survived. The median survival time was 6.5 months (196 days). Grade 3 or higher adverse events included hypertension (12.73%), leukopenia (3.64%), absolute neutropenia (1.82%), thrombocytopenia (9.09%), fatigue (3.64%), anemia (1.82%), and diarrhea (1.82%). Adverse events were effectively controlled. One case had fatal ruptured esophageal varices, which were not medically related. Multivariate Cox regression analysis showed that total bilirubin (HR = 0.247, P = 0.003), albumin (HR = 0.279, P = 0.003) and procalcitonin (HR = 0.105, P = 0.012) were independent factors affecting the prognosis of advanced HCC. Conclusion: Anlotinib hydrochloride therapy is safe, effective and well tolerated in patients with advanced liver cancer, and total bilirubin, albumin, and procalcitonin are independent factors that affect the prognosis of patients with advanced liver cancer.

Multilocus sequence typing analysis of Candida africana from vulvovaginal candidiasis.

BACKGROUND: Candida africana is distributed worldwide and colonized in human genitalia and cause mainly vulvovaginal candidiasis (VVC). We report the multilocus sequence typing (MLST) analysis of C. africana from VVC. METHODS: MLST analysis of 43 strains of C. africana, which were isolated from vaginal specimens of patients with VVC, was performed. The enzymatic activity of phospholipase, esterase and haemolysis enzyme production was evaluated.The level of virulent genes and resistant genes mRNA expression was determined by using real-time PCR. Antifungal susceptibilities of the isolates were assayed by using the broth microdilution method. The statistical of the results was determined by the T test and Pearson chi-squared test. RESULTS: The MLST analysis revealed a substantial degree of genetic homogeneity. The DST782 and DST182 were the main MLST genotypes in C. africana. All the patients were symptomatic and with a high mycological cure rate when treated with commonly used antifungal agents.There were statistically significant differences in biofilm formation and phospholipase activity between C. africana and C.albicans. The level of virulent genes and resistant genes mRNA expression was higher in fluconazole-resistant strains. All C. africana isolates were susceptible to fluconazole, itraconazole, voriconazole, caspofungin, and micafungin. These isolates also exhibited low MICs to amphotericin B, flucytosine, and posaconazole. CONCLUSIONS: Candida africana appear to be with a low level of sequence variation in MLST loci. Candida africana, a lower virulence candida, is susceptible to commonly used antifungal agents. This paper was presented at the conference of 8th Trend in Medical Mycology (6-9 October 2017, Belgrade, Serbia) and was published on conference abstract.

[Risk factors and sonographic findings associated with the type of placenta accreta spectrum disorders].

Objective: To evaluate the risk factors and sonographic findings of pregnancies complicated by placenta increta or placenta percreta. Methods: Totally, 2 219 cases were retrospectively analyzed from 20 tertiary hospitals in China from January 2011 to December 2015. The data were collected based on the original case records. All cases were divided into two groups, the placenta increta (PI) group (79.1%, 1 755/2 219) and the placenta percreta (PP) group (20.9%, 464/2 219) , according to the degree of placental implantation. The risk factors and sonographic findings of placenta increta or percreta were analyzed by uni-factor and logistic regression statistic methods. Results: The risk factors associated with the degree of placental implantation were age, gravida, previous abortion or miscarriage, previous cesarean sections, and placenta previa (all P<0.05), especially, previous cesarean sections (χ(2)=157.961) and placenta previa (χ(2)=91.759). Sonographic findings could be used to predict the degree of placental invasion especially the boundaries between placenta and uterine serosa, the boundary between placenta and myometrium, the disruption of the placental-uterine wall interface and loss of the normal retroplacental hypoechoic zone(all P<0.01). Conclusions: Previous cesarean sections and placenta previa are the main independent risk factors associated with the degree of placenta implantation. Ultrasound could be used to make a prenatal suggestive diagnosis of placenta accreta spectrum disorders.

In vitro fluconazole and nystatin susceptibility and clinical outcome in complicated vulvovaginal candidosis.

To correlate fluconazole and nystatin susceptibility with clinical outcome for complicated vulvovaginal candidosis (VVC), 287 Candida isolates were collected from 283 patients with complicated VVC. In vitro fluconazole and nystatin susceptibility was tested using E-test or commercial agar diffusion method. The patients were treated with fluconazole or nystatin. The fluconazole-resistant and -susceptible dose-dependent (SDD) rates of Candida species were 0.8% (1/132) and 5.3% (7/132) respectively. The mycological cure rate at days 7-14 and days 30-35 in fluconazole SDD isolates was lower than that in fluconazole-susceptible isolates (42.9% vs. 88.7% and 28.6% vs. 76.6%, P < 0.05). The mycological cure rate at days 7-14 and days 30-35 in VVC caused by Candida albicans and non-albicans Candida species was 85.6% (219/256) vs. 88.9% (24/27) and 79.3% (203/256) vs. 81.5% (22/27), P > 0.05. All C. albicans and non-albicans Candida species were susceptible to nystatin in vitro. The mycological cure rate of the patients treated with nystatin at days 7-14 and days 30-35 in VVC was 85.4% (129/151) and 83.4% (126/151) respectively. We conclude that fluconazole resistance was rare and both C. albicans and non-albicans Candida species were susceptible to nystatin in vitro. The decrease in fluconazole susceptibility or a low concentration of fluconazole in the vagina was probably related to fluconazole therapeutic failure.

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.

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.

Methylrosaniline chloride stained vaginal smears for the diagnosis of vulvovaginal candidiasis.

OBJECTIVE: To study the sensitivity and specificity of methylrosaniline chloride stained vaginal smears for the diagnosis of vulvovaginal candidiasis (VVC). METHOD: Between September 2005 and February 2006, 214 cases of patients with VVC and 102 cases of controls were investigated at Peking University Shenzhen Hospital. All strains were identified with the API Candida system. RESULTS: The average age of the patients was 29.87 years. The sensitivity and specificity of methylrosaniline chloride stained vaginal smears for the diagnosis of vulvovaginal candidiasis were 88.3% (189/214) and 96.1 (98/102). The sensitivity of the vaginal smears for the diagnosis of recurrent vulvovaginal candidiasis, mild vulvovaginal candidiasis and severe vulvovaginal candidiasis were 85.2% (46/54), 74.7% (71/95) and 99.2% (118/119). CONCLUSION: Methylrosaniline chloride stained vaginal smears for the diagnosis of vulvovaginal candidiasis are reliable and inexpensive.

Squalene inhibits sodium arsenite-induced sister chromatid exchanges and micronuclei in Chinese hamster ovary-K1 cells.

Arsenic, widely distributed throughout our environment, is a well-established human carcinogen. We report here that squalene, a natural fish oil, is a potential agent in the reduction of sodium arsenite-induced sister chromatid exchange (SCE) and micronuclei in Chinese hamster ovary (CHO-K1) cells. Squalene dose-dependently inhibited sodium arsenite-induced SCE. At the highest concentration (160 microM), squalene reduced the SCE frequency from 8.85 to 6.47 SCEs per cell which is very close to the background level (5.82 SCEs per cell). Sodium arsenite dose-dependently induces micronuclei in CHO-K1 cells, and squalene at 80 microM significantly inhibits arsenite-induced micronuclei. However, squalene did not eliminate the killing effects of arsenite on the cells and only slightly decreased intracellular accumulation of arsenic.

[Detection of human papillomavirus DNA and clinicopathological study of vulvar human papillomavirus infection].

We studied 217 vulvar HPV infection patients by clinically, pathologically, and virologically. From 90.6% of the cauliflower-like vulvar lesions and 29.7% of the papillomatous and finger-like lesions, we detected HPV 6/11 DNA by dot blotting hybridization. The patients in 90.0% of the cauliflower-like group and 9.8% of the papillomatous and finger-like group had a high risk factor to intercourse with different sex partners (P < 0.0001). The pathological characteristics, nature history, and response to treatment were different. According to clinical, pathological, and virological findings divided three types: vulvar HPV infection type 1 (or condylomata acuminata), vulvar HPV infection type 2, and vulvar HPV infection type 3.

[The influence of internal fetal monitoring on pregnancy outcome and survey of uterine contraction].

Pregnancy outcome of 30 primigravida receiving internal fetal monitoring (IFM) was studied with 52 cases without IFM as control. Intrauterine pressure was measured in IFM patients during active phase and second stage of labor. The occurrence of fetal distress, neonatal morbidity and the positive isolation rate of bacteria in amnionic fluid and aspirate from the throat of newborns was 56.7%, 23.3%, 50.0% and 45.5% respectively in the IFM group. The occurrence of fetal distress and neonatal morbidity were significantly higher than those of the control group. The intrauterine pressure, duration, frequency and intensity of uterine contractions during active phase and second stage of labor were observed. The characters of uterine contraction in IFM and external fetal monitoring were different, and a kind of false fetal heart rate deceleration was described in the paper.

[A prospective study of maternal-infant transmission of Chlamydia trachomatis].

Direct immunofluorescent monoclonal antibody test was used for the examination of Chlamydia trachomatis at the cervices of 130 pregnant women and women after deliveries for 2-6 months with extragenital condyloma acuminatum and at the palpebral conjunctivae of their 102 newborns and infants. The results show that the rate of cervical infection in pregnant women is 4.92% and the rate of palpebral infection in the newborns 8.57%. After postnatal 2-6 months, the rates were markedly decreased both in the mothers and their infants, being 1.45% and 0%, respectively. Chlamydia trachomatis infection is a new topic in modern perinatal medicine. In the report, the prevention of maternal-infant transmission problem was discussed.

Species distribution and susceptibility of Candida isolates from patient with vulvovaginal candidiasis in Southern China from 2003 to 2012.

OBJECTIVE: To determine the Candida species involved and the antifungal susceptibility of Candida species isolated from patients with vulvovaginal candidiasis (VVC). MATERIALS AND METHODS: Candida organisms were cultured from samples obtained from patients with VVC at Gynecology Department of Peking University Shenzhen Hospital from April 2003 to September 2012. Antifungal susceptibility testing was performed using a commercial agar diffusion test. RESULTS: A total of 3181 yeasts isolates, mostly Candida, were obtained from 3141 patients with VVC. Two species of Candida were isolated from each of 40 patients (1.3%, 40/3141). C. albicans were the predominant Candida species (2705 strains, 85.0%) in VVC, followed by C. glabrata (337 strains, 10.6%), C. parapsilosis (49 strains, 1.5%), C. tropicalis (31 strains, 1.0%), Saccharomyces cerevisiae (23 strains, 0.7%), C. krusei (15 strains, 0.5%), Candida famata (11 strains, 0.4%), Rhodotorula sp. (6 strains, 0.2%), and C. lusitaniae (2 strains, 0.1%). Antifungal susceptibility was tested in a total of 1942 strains from patients with VVC. All of the C. albicans isolates obtained were susceptible to nystatin. The resistant rate of C. albicans to fluconazole, itraconazole, miconazole, clotrimazole was 1.1% (18/1612), 2.2% (36/1612), 4.2% (68/1612), and 0.9% (14/1612). The resistant rate of non-albicans to fluconazole, itraconazole, miconazole, and clotrimazole was 11.8% (39/329), 2.5% (8/329), 1.8% (6/329), and 4.3% (14/329). CONCLUSIONS: C. albicans was the predominant Candida species isolated from this series of patients with VVC. Resistance of vaginal C. albicans isolates to antifungal agents was infrequent.