Fufan Zhu’s research while affiliated with The Second Xiangya Hospital of Central South University and other places

Background: Early diagnosis is important to lower the mortality rate of acute fatty liver of pregnancy (AFLP). The Swansea criteria is commonly used to diagnose AFLP, but some terms could only be reached when symptoms and signs have progressed, or are not efficient in clinical practice. Therefore, it is necessary to select cost effective tests to simplify and facilitate early suspicion of acute fatty liver of pregnancy. Methods: This is a retrospective study of 28,800 medical records at the Second Xiangya Hospital from 2009 to 2015, including 41 patients with AFLP and 172 other diseases that could show similar symptoms to AFLP. The evaluated variables included past history of liver diseases, blood pressure, gastrointestinal symptoms, blood count, liver function test, coagulation function test and blood sugar test. The sensitivity, specificity, positive predict value and negative predict value were calculated for models in diagnosing AFLP. Results: The significant variables associated with AFLP included gastrointestinal symptoms, blood pressure > 140/90 mmHg, aminotransferase> 42 IU/l, total bilirubin> 0.8 mg/dl, total bilirubin acid> 10.0 μmol/L, activated partial prothrombin time(APTT) > 34 s, prothrombin time(PT) > 14 s, white blood cells> 11 *106/l and blood sugar< 72 mg/dl. Gastrointestinal symptoms +aminotransferase +bilirubin +bile acid +APTT/PT showed 97.6% sensitivity and 97.1% specificity to diagnose AFLP. Adding blood pressure, blood sugar or white blood cells decreased the accuracy of the statistical model. Conclusions: Application of a statistical model including maternal symptoms, biochemical and haematological parameters has high diagnostic accuracy for earlier identification of AFLP. However, this finding needs to be tested in another cohort to determine whether this statistical model has the same performance.

Objective: To explore the effect of adipose-derived mesenchymal stem cells (ADMSCs) on ovarian damage induced by cyclophosphamide (CTX) and its mechanism. Methods: ADMSCs isolated from adipose tissue of female SD rats were cultured and divided into a blank group and a CTX group (n=15 in each group). CTX (75 mg/kg) was injected intraperitoneally to establish a model of ovarian damage in rats. A total of 45 female SD rats were also divided into 3 groups: Group A (15 rats, only injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline), Group B [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 0.6 mL ADMSCs (6×105 cells) by the tail vein], and Group C [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 40 mL ADMSCs (20 mL per side, 2×104 cells) in situ ovarian]. After 4 estrus cycles, the changes of quality of life, ponderal growth were recorded, the sex hormone levels [estradiol (E2), follicle-stimulating hormone (FSH)] were tested by ELISA, and the morphology of ovarian tissue and follicle count were observed by HE staining. The expression of BMP-15, Bcl-2 and Bax in ovarian tissues were tested by immunohistochemistry, real-time PCR or Western blotting. The apoptosis rate of follicular cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay. Results: After transplantation of ADMSCs, compared with the Group A, their quality of life of rats in the Group B and C was improved, and the ponderal growth was increased (both P<0.01). Compared with the Group A, the serum E2 levels in the Group B and the Group C were increased (P<0.01, P<0.05), and the FSH levels in the Group B and C were decreased (both P<0.01). The granular cell layer, the number of corpus lutein and the count of various grade follicles were significantly increased, and many new follicles and mature oocytes were observed in the Group B and C. Compared with Group A, the count of primitive follicles, sinusoidal follicles, pre-ovulation follicles and total follicles, and pre-sinusoidal follicles were dramatically increased in the Group B. The follicle at all levels count was increased in the Group C than that in the Group A (all P<0.01). Comparing with the Group A, the expressions of BMP-15 and Bcl-2 were increased (all P<0.01), the expressions of Bax was decreased (both P<0.01), and the apoptosis rates of follicular cells were decreased in the Group B and C (both P<0.01). However, there was no difference between the Group B and the Group C in the above indexes (all P>0.05). Conclusion: ADMSCs transplantation can effectively repair ovarian damage induced by CTX in rats, which may be achieved by inhibiting mitochondrial apoptosis of granulosa cells.

Preeclampsia is a common disease in pregnant women that can only be diagnosed from 20 weeks after fertilization. Developing early diagnosis markers is urgent and would be helpful in selecting appropriate treatment strategies. The present study aimed to identify the differential expression profiles of microRNAs in the plasma between patients with preeclampsia and normal pregnancies using microarray methods. Using quantitative polymerase chain reaction (qPCR), the differentially expressed microRNAs (miRNAs or miRs) identified from the microarray analysis were validated. A total of 3 miRNAs, including hsa-miR-1304-5p, hsa-miR-320a and hsa-miR-5002-5p, were upregulated in the plasma of patients with preeclampsia pregnancies. Examination of the functions of these miRNAs demonstrated that they were involved in cell proliferation, indicating that preeclampsia affected this pathway. In addition, 26 downregulated miRNAs were identified by microarray methods. The functions of these miRNAs included immune regulation, vascular development, cancer pathology and pathology of other disease (tuberculosis, oligozoospermia, psoriasis and Alzheimer's disease). Using qPCR, the most differentially expressed miRNAs were confirmed to be hsa-miR-1304-5p, hsa-miR-320a and hsa-miR-5002-5p, which were upregulated, as well as hsa-miR-188-3p, hsa-miR-211-5p, hiv1-miR-TAR-3p, hsa-miR-4432 and hsa-miR-4498 that were significantly downregulated in the plasma of preeclampsia patients. The present findings may be useful in the development of early diagnosis markers and treatment targets for preeclampsia.

Early assessment before the establishment of placental dysfunction has the potential to improve treatment and prognosis for clinical practice.The objective of the study is to investigate the accuracy of serum biochemical markers(Pregnancy- Associated Plasma Protein-A (PAPP-A), human Chorionic Gonadotropin (hCG), Placental Growth Factor (PlGF), Placental Protein 13 (PP13) used in first trimester serum screening in predicting preelampsia, small for gestational age (SGA) and preterm delivery. The data sources included Medline, Embase, Cochrane library, Medion, hand searching of relevant journals, reference list checking of included articles and contact with experts. Two reviewers independently selected the articles. Two authors independently extracted data on study characteristics, quality and results. The results showed low predictive accuracy overall. For preeclampsia, the best predictor was PlGF; LR + 4.01 (3.74, 4.28), LR-(0.67, 0.64, 0.69). The predictive value of serum markers for early preeclampsia was better than that of late preeclampsia. For SGA the best predictor was PP13; LR+ 3.70 (3.39, 4.03), LR- 0.70 (0.67, 0.73). For preterm delivery, the best predictor was PP13; LR+ 4.16 (2.72, 5.61), LR- 0.56 (0.45, 0.67). First trimester screening analytes have low predictive accuracy for pre-eclampsia, small for gestational age and preterm delivery. However, the predict value of first trimester analytes is not worse than that of the second trimester markers.

Steroid cell tumors not otherwise specified (NOS) are a rare subgroup of sex cord-stromal tumors. The tumors can occur at any age, although the mean age of occurrence is 43 years old. The majority are benign, but have the capability of producing one or more steroids associated with virilization. The present study reports the case of a 29-year-old female who presented to the Second Xiangya Hospital suffering from lower back and leg pain that had persisted for five months. The patient had regular menstrual cycles and no virilization symptoms were present. Laboratory investigations revealed normal hormone levels. Multiple areas of bone destruction and a right ovarian mass were confirmed via positron emission tomography/computed tomography. The patient underwent an exploratory laparotomy, and a mass measuring ~6 cm in diameter was subsequently identified in the right ovary. A right salpingo-oophorectomy and pelvic washings for cytology were performed. Histopathological studies confirmed the diagnosis of a malignant steroid cell tumor NOS of the right ovary. The patient underwent eight cycles of chemotherapy (docetaxel, 120 mg and nedaplatin, 80 mg). The patient continued to have relatively good health, with no deterioration of the condition for one year and a half, however, the disease progressed and the patient succumbed to brain metastases six months later.

Objectives: To compare serum chemerin levels between women with classic hyperandrogenic PCOS, euandrogenic PCOS and matched control subjects. Research design and methods: This study was carried out at the Second XiangYa Hospital between July 2012 and April 2013. Sixty-seven women with PCOS and 20 controls were included. Blood pressure, body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting plasma glucose and blood serum hormone and blood lipid were measured. Transvaginal ultrasound was performed. Serum chemerin was measured by ELISA. Results: Serum chemerin was significantly higher in classic hyperandrogenic PCOS compared with euandrogenic PCOS and controls (311.07 ± 141.87 ng/mL versus 228.03 ± 119.66 ng/mL and 225.87 ± 86.44 ng/mL, p < 0.05). Serum chemerin was positively related to follicle count, ovarian volume, the level of testosterone, luteinizing hormone/follicle-stimulating hormone, low-density lipoprotein, triglycerides, fasting blood insulin, insulin resistance by homeostasis model assessment, WHR and BMI, while negatively related to the level of high-density lipoprotein. Multiple linear regression analyses revealed ovarian volumes and WHR were the significant influencing factors of chemerin (p < 0.05). The area under the receiver operating characteristic curve for chemerin reached a value of 0.684 (0.572-0.796, 95% confidence interval). The best compromise between sensitivity (80.0%) and specificity (47.6%) was obtained with a cutoff value of 200.94 ng/mL. Conclusions: Serum chemerin level was increased in Chinese women with classic hyperandrogenic PCOS. Serum chemerin measurement offers a relatively moderate diagnostic potency with a sensitivity of 80.0% and a specificity of 47.6% at 200.94 ng/mL. This suggested that chemerin may be involved in the development of the metabolic syndrome of classic PCOS.

Objective: To evaluate the safety, effectiveness and complications of serial invasive prenatal diagnostic techniques, and to investigate the prenatal diagnosis indication as well as to analyze the abnormal chromosomal karyotype. Methods: We retrospectively studied all patients from March 2005 to May 2012 who received amniocentesis and cordocentesis in the prenatal diagnosis center of Second Xiangya Hospital. The indication of the procedure, successful rate and complications were evaluated, and 25 abnormal chromosome nuclear types were analyzed. Results: A total of 669 patients received invasive prenatal diagnosis from March 2005 to May 2012 in Second Xiangya Hospital: 598 received amniocentesis and 71 cordocentesis carried out. Compared with the cordocentesis group, the amniocentesis group had higher achievement ratio (91.54% vs 100%, P<0.05), lower spontaneous abortion rate (1.41% vs 0.33%, P<0.05), fewer abnormal karyotypes (11.27% vs 2.84%, P<0.05) and lower expenditure (880 yuan vs 800 yuan, P<0.05). Positive screening, advanced maternal age, and ultrasonography abnormality were the top 3 indications of amniocentesis and cordocentesis. We found 25 abnormal karyotypes, including 6 cases of trisomy 21, 4 sex chromosomal abnormalities, 7 autosomal balanced translocations, 1 marker chromosome, and 7 mosaics. Conclusion: As a widely used invasive prenatal diagnosis, amniocentesis is safe and effective. The complications of cordocentesis are much higher than those of amniocentesis, which is not a proper routine procedure for prenatal diagnosis of abnormal karyotype. The analysis of karyotype not only can identify fetal chromosome abnormality, but also provide the scientific basis for pregnancy continuation, thus reducing the ratio of birth defect.

Aim: To investigate the adverse effects of alcohol on ovarian reserve in women of childbearing age. Material and methods: Twenty bar hostesses between the ages of 18 and 29 with moderate alcohol consumption for over 3 years and 16 healthy women between the ages of 18 and 28 with alcohol consumption under a healthy standard were recruited. Their ovarian reserve was evaluated by measuring menstrual cycle day three (CD3) serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL) and testosterone (TST) levels, and by transvaginal B-ultrasound examination of uterine size, ovarian size and number of antral follicles. Results: Moderate consumption of alcohol significantly increased serum FSH level (P=0.001), but had no effect on serum LH, E2, PRL and TST levels. Moderate alcohol consumption significantly decreased ovarian volume (P=0.000) and number of ovarian antral follicles (P=0.015), but had no effect on uterus size. Moderate alcohol consumption significantly increased the occurrence of menstrual flow abnormalities (P=0.001 and P=0.036, respectively), but had no effect on menstrual cycle. The amount of alcohol consumed positively correlated with FSH, and negatively correlated with ovarian volume and number of antral follicles in women with moderate alcohol consumption. Conclusion: Long-term moderate alcohol consumption may lead to diminished ovarian reserve.

The aim of this study was to evaluate the effect of traditional treatment (prednisone and aspirin) and comprehensive treatment [prednisone, aspirin, low molecular weight heparin (LMWH) and IVIg] on the pregnancy outcome, obstetric complications and fetal outcome in women with antiphospholipid syndrome (APS). In the present trial, we observed and evaluated 129 women with APS. Eighty-seven patients received traditional treatment and 42 patients received comprehensive treatment. In the traditional treatment group and comprehensive treatment group, the live birth rate was 83.91 and 97.62% (P<0.05), respectively, and the obstetric morbidity was 22.99 and 7.14% (P<0.05), respectively. The neonatal weight in the comprehensive treatment group was increased compared with the traditional treatment group (P<0.05), however, no differences were found in gestational age at delivery or preterm labor. Comprehensive treatment improved the result of gestation and reduced obstetric complications, and is a more effective treatment for APS than the traditional method using prednisone and aspirin.

A nano-structured scaffold was designed for bone repair using collagen, hyaluronic acid (HYA) and nano-bioactive glass (NBaG) as its main components. The collagen-HYA/NBaG scaffold was prepared by using a freeze-drying technique and characterized by scanning electron microscopy (SEM). Osteoblastls were seeded on these scaffolds and their proliferation rate, alkaline phosphatase (ALP) activity and ability to form mineralized bone nodules were compared with those osteoblasts grown on cell culture plastic surfaces. The cross-section morphology shows that the collagen-HYA/NBaG scaffold possessed a three-dimensional (3D) interconnected homogenous porous structure. The results obtained from biological assessment show that this scaffold did not negatively affect osteoblasts proliferation rate and improves osteoblasts function as shown by increasing the ALP activity and calcium deposition and formation of mineralized bone nodules. Therefore, the composite scaffolds could provide a favorable environment for initial cell adhesion, maintained cell viability and cell proliferation, and had good In-Vitro biocompatibility.