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Study question Does anti-Mullerian hormone (AMH) inhibit activation (initiation of growth) of primordial follicles and attenuate the growth of primary follicles in cattle, an excellent animal model for human ovarian follicular development? Summary answer AMH inhibited activation of bovine primordial follicles and attenuated the growth of activated follicles in vitro. What is known already In mice null mutant for AMH, the pool of primordial follicles is depleted prematurely and AMH inhibits follicle activation in vitro. Results of studies with human ovarian tissue in vitro were inconsistent. Our previous work provided indirect evidence that AMH inhibits follicle activation in bovine ovaries. Study design, size, duration Pieces of fetal bovine ovarian cortex (2 pieces/culture well), obtained during mid or late pregnancy, were cultured in control medium or with graded doses of AMH for 2, 10 or 12 days. Effects of treatment on follicle activation and growth were determined by histological morphometry; follicles in every 20th histological section were staged (primordial or primary), counted, and measured. In addition, AMH was immunolocalized in bovine ovaries obtained at various times during pregnancy (n = 20 ovaries). Participants/materials, setting, methods Bovine fetal ovaries at mid or late gestation were obtained at a commercial abattoir. Pieces of ovarian cortex were cultured without or with AMH and fixed for histological morphometry on Day 0 and at the end of culture. Treatments were applied to duplicate cultures from each of two or three fetuses. In 12-day cultures, addition of AMH was delayed until the third day. Histological analysis provided information about the types, numbers and sizes of follicles in cortical pieces before and after treatments. Ovaries obtained during the second and third trimesters were assessed for the presence of AMH by immunohistochemistry. Main results and the role of chance AMH (100-500 ng/ml) inhibited follicle activation in response to an activator (insulin) in ovarian cortical pieces from fetal ovaries in late gestation. Dose-dependent inhibitory effects on the diameters of primary follicles and their oocytes were also observed. These results were obtained only when AMH was added to cultures in advance of insulin (presumably because it penetrates tissue more slowly than insulin). Results of experiments with cortical pieces from fetal ovaries at mid-gestation, when follicles are forming, showed that AMH did not inhibit the formation of follicles. Immunohistochemical localization of AMH showed that it is not present in fetal ovaries until the third trimester, when it was localized to the granulosa cells of secondary and small antral follicles. Limitations reasons for caution The experiments were performed with fetal ovaries because follicles form and follicle activation begins during fetal life in cattle (as it does in humans), so fetal ovarian cortex of later gestation provides tissue rich in primordial follicles. We assume, but have no experimental evidence, that our findings also apply to post-natal ovaries. Wider implications of the findings Although circulating AMH is used as an indication of the follicular reserve in women, little is known about AMH in human ovaries. Cattle are an excellent non-primate model for human ovarian follicular development and, hence, the findings suggest similar roles for AMH in human follicular development. Large scale data Not applicable. Study fundng/competing interest(s) This research was supported by National Research Initiative Competitive Grants no. 00-35203-9151, 2003-35203-13532, and 2008-35203-05989) from the U.S. Dept. of Agriculture's National Institute of Food and Agriculture to JEF and by an NIH National Research Service Award (F32 HD08264) to RAC. There are no conflicts of interest or competing interests.

OBJECTIVE: To establish predictive models based on random forest and XGBoost machine learning algorithm and to investigate their value in predicting early stone-free rate (SFR) after flexible ureteroscopic lithotripsy (fURL) in patients with renal stones. METHODS: The clinical data of 201 patients with renal stones who underwent fURL were retrospectively investigated. According to the stone-free standard, the patients were divided into stone-free group (SF group) and stone-residual group (SR group). We compared a number of factors including patient age, body mass index (BMI), stone number, stone volume, stone density and hydronephrosis between the two groups. For low calyceal calculi, renal anatomic parameters including infundibular angle (IPA), infundibular width (IW), infundibular length (IL) and pelvic calyceal height (PCH), would be measured. We brought above potential predictive factors into random forest and XGBoost machine learning algorithm respectively to develop two predictive models. The receiver operating characteristic curve (ROC curve) was established in order to test the predictive ability of the model. Clinical data of 71 patients were collected prospectively to validate the predictive models externally. RESULTS: In this study, 201 fURL operations were successfully completed. The one-phase early SFR was 61.2%. We built two predictive models based on random forest and XGBoost machine learning algorithm. The predictive variables’ importance scores were obtained. The area under the ROC curve (AUROC) of the two predictive models for early stone clearance status prediction was 0.77. In the study, 71 test samples were used for external validation. The results showed that the total predictive accuracy, predictive specificity and predictive sensitivity of the random forest and XGBoost models were 75.7%, 82.6%, 60.0%, and 81.4%, 87.0%, 68.0%, respectively. The first four predictive variables in importance were stone volume, mean stone density, maximal stone density and BMI in both random forest and XGBoost predictive models. CONCLUSION: The predictive models based on random forest and XGBoost machine learning algorithm can predict postoperative early stone status after fURL for renal stones accurately, which will facilitate preoperative evaluation and clinical decision-making. Stone volume, mean stone density, maximal stone density and BMI may be the important predictive factors affecting early SFR after fURL for renal stones.

We integrated all the eligible studies and investigated whether the TNF-α 308G/A polymorphism correlates with urogenital cancer risk. Tumor necrosis factor-α (TNF-α) is a risk factor for some urogenital cancers; however, in prostate and bladder cancers the results are controversial. PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database were searched for all case-control studies on the relationship between the TNF-α 308G/A polymorphism and susceptibility to urogenital cancer between January 1994 and January 2015. The pooled odds ratio with 95% confidence interval was calculated to assess the associations. A total of 504 articles were found, 39 of which involved 11,613 cases and 12,542 controls that fulfilled the inclusion criteria. Overall, the TNF-α 308G/A polymorphism was significantly associated with the risk of urogenital cancer. In the subgroup analysis for different cancer types, significant associations were found in cervical cancer and urothelial carcinoma, while our meta-analysis indicated that there were no significant associations between the TNF-α 308G/A polymorphism and prostate, bladder, or renal cancers. When stratified by ethnicity, significant associations were observed in Caucasian populations, whereas no significant associations were found in African-Americans, Asians, or mixed populations. Furthermore, carriers of the -308A allele among the hospital-based case-control group were at a high risk of urogenital cancer. Our meta-analysis showed that the TNF-α 308G/A polymorphism was significantly associated with urogenital cancer risk, particularly in the Caucasian and hospital-based populations.

Haemophilia is uncommon in females and little is known about the clinical manifestations and postpartum management of women with this disorder. Clinical characteristics of postpartum bleeding were evaluated in women with factor IX deficiency (FIX:C0.20 U mL(-1)), including two with haemophilia B and three carriers of haemophilia B, undergoing labour and delivery. Data were collected prospectively during routine outpatient comprehensive haemophilia care at the haemophilia Center of Western Pennsylvania and during inpatient management. Four of five women experienced postpartum bleeding, during six of 16 deliveries: the median haemoglobin was 10.7 g% and two required blood transfusion. Postpartum bleeding was significantly more common among those receiving fewer than 4 days of FIX replacement: six of 13 (46.1%) receiving fewer three or fewer days bled vs. none of three (0%) receiving six or more days treatment [P01 (Wilcoxon)]. Postpartum bleeding was not related to the route of delivery (P = 0.525), vaginal vs. Caesarean, nor the FIX level (P = 0.371; FIX0.05 U mL(-1) vs.or =0.05 U mL(-1)). Compared with females with von Willebrand disease or FXI deficiency, females with FIX deficiency were more likely to experience postpartum bleeding (P = 0.008) and anaemia (P = 0.045); and they were less likely to experience menorrhagia (P = 0.065), but the latter did not reach significance. Postpartum bleeding is common in women with haemophilia B or carriers of haemophilia B, and treatment with factor replacement for at least 4 days of postpartum may prevent bleeding following delivery in such women.

Hepatocellular carcinoma is commonly found in Asian countries and prognosis still remains unsatisfactory due to recurrence after surgical tumor resection.We try to demonstrate the recurrence and survival time in 99 surgical patients grading by tumor cellular differentiation from surgical specimen.The rates of well, moderate, and poor differentiation were encountered in 21 cases (21.2%), 61 cases (61.6%) and 17 cases (17.7%), respectively. Small tumor (3 cm) was found in only one (5.9%) in the poor differentiation group and 38.1% and 37.7% in the well and moderate differentiation groups. Capsular invasion was found in 13 (61.9%), 39 (63.9%) and 7 (41.1%) in the well, moderate and poor differentiation group, respectively. We found 41.9% (18/43) and 22.4% (13/58) to be tumor free in capsule invasion (-) and (+) after a period of 18.1 and 29.9 months, respectively. However, the recurrent time was 10.6 and 11.3 months, respectively with no significant difference (p0.05). Vascular invasion was more frequent in the poor differentiation group (76.5%) than the well (23.8%) and moderate (60.7%) differentiation groups (P0.05). We found 23.5% (4/17) and 35% (21/60) to be tumor free but the recurrence time was 6.5 and 14.1 months for the vascular invasion (-) and (+), respectively. The residual median survival times were 6.5 and 14 months after recurrence, respectively. The tumor recurrence rates were 52.7% (11/21), 52.4% (32/61), and 35.5% (6/17) and recurrence times were 11.7, 11.9, and 4.5 months for the well, moderate and poor differentiation group respectively totally. The recurrence time of young age group (39 years old) was shorter than the others and there was no patient of well differentiation less than 40 years old. The recurrence time was shorter in the poor differentiation group but there was no significant difference according to age group. The median survival times were 22.2, 22.9, and 9.5 months for each group, respectively.Differentiation of hepatocellular carcinoma cell had a clinical significance and was found to be positively correlated with the invasive proclivity. The median survival time was longer in both the well and moderate differentiation group, but not in the poor differentiation group. The clinical data revealed that the extended operations performed upon the patients with poor differentiation effected the recurrence time but not the survival time.

To probe into the methods and effects of small soft tissue defect of facial area, nose and eyelid repaired by temporal island flap pedicled with orbicularis oculi muscle.From 1994 to 1999, 12 cases with cicatricial ectropion of eyelid, scar in nose and facial area or facial mole were repaired by temporal flap pedicled with orbicularis oculi muscle. The maximal area of skin flap was 3 cm x 5 cm.All the skin flaps were survived after operation. Six cases were followed up from 6 months to 4 years, the results were satisfied. There were no secondary deformity or scar formation in the donor site.The blood supply of orbicularis oculi muscle is plentiful. It is a reliable method to repair of small facial tissue defect using temporal island flap pedicled with orbicularis oculi muscle. But in bigger facial soft tissue defect, it should be cautious.

This case study reported a 17-year-old female of common variable immunodeficiency (CVID) associated with bronchiectasis, pernicious anemia and mosaic trisomy 8. Clinically this patient presented with recurrent sinopulmonary infections, intractable diarrhea, macrocytic anemia, and primary amenorrhea. Immunological tests showed pan-hypogammaglobulinemia and a decrease of peripheral blood B cells (4%) and CD4+ cells (25%). Lymphoproliferative responses to mitogen (PHA) and specific antigen (BCG) were profoundly impaired in the patient in comparison to those in control. Production of interleukin 4 (IL-4) and gamma interferon (IFN-gamma) in the in vitro lymphoproliferation was also profoundly depressed. Pernicious anemia demonstrated by larger MCV (112.9 fl) and hyper-segmental granulocytes on peripheral blood smear responded to parental administration of vitamin B12. Interestingly, she had a mosaic trisomy 8 in peripheral blood mononuclear cells but normal 46XX karyotype in the bone marrow cells. To our knowledge, this is the first case of CVID associated with mosaic trisomy 8 reported in the literature. As the case exemplifies, CVID should be considered when the physicians evaluate the patient presenting with recurrent sinopulmonary infections, diarrhea, malnutrition, and pernicious anemia. It requires further study to explore whether the genes in the chromosome 8 are linked to CVID.

Antibody-dependent enhancement has been implicated in some outbreaks of epidemic dengue hemorrhagic fever, however, the mechanism of antibody-dependent enhancement is not well known. This study was conducted to investigate the cross-protection and cross-enhancement of dengue-2 virus infections by dengue-1 immune sera. It was found that dengue-1 immune sera at 1:5 dilution (n = 12) could neutralize dengue-2 infections in BHK-21 cells, as assessed by a standard plaque-reduction neutralization assay. Two-thirds of the dengue-1 immune sera at 1:25 dilution demonstrated neutralizing effects for dengue-2 infections, whereas, non-immune sera revealed no neutralization for dengue-2 infections in BHK-21 cells. Human mononuclear leukocytes in response to dengue-2 infections elicited a T cell helper 1 (Th1) response revealing induction of IFNgamma but not IL-4 production. Dengue-1 immune sera did not neutralize dengue-2 infections in mononuclear leukocytes. Subneutralizing titers of dengue-1 immune sera at 1:250, but not at 1:10 dilution, enhanced dengue-2 infections in mononuclear leukocytes (1.2 +/- 0.7 x 10(4) vs. 2.8 +/- 0.3 x 10(2) PFU/ml). The enhancement of dengue-2 infections in mononuclear leukocytes by dengue-1 immune sera at 1:250 was associated with an increase in the lymphocyte proliferation index, and a decrease in IFNgamma production (56 +/- 24 vs. 12 +/- 3 pg/ml). The addition of IFNgamma (0.1 microg/ml) suppressed significantly the antibody-dependent enhancement induced by dengue-1 immune sera, whereas the presence of anti-IFNgamma F(ab)2 antibody augmented the antibody-dependent enhancement effect. Results from this study suggest that suppression of Th1 response may be involved in the antibody-dependent enhancement of heterotypic dengue infections. Better regulation of Th1/Th2 reactions may be useful for prevention of heterotypic immune enhancement of dengue infections.

In view of cytokine's effects in promoting or inhibiting inflammation, the objective of this study was to explore the characteristics of the proinflammatory cytokine, interleukin-8 (IL-8), and the inhibitory cytokine, interleukin-10 (IL-10), in the bronchoalveolar lavage (BAL) fluid of premature infants suffering from respiratory distress disease. Eighteen premature neonates with respiratory distress disease with gestational age (GA) ranging from 24 to 37 weeks were recruited for study. BAL fluids were collected following endotracheal intubation during an episode of hypoxemia or dyspnea. A series of BAL samples were obtained on day 1, 2, 4 and 7 after intubation for measuring IL-8 and IL-10 levels. The results indicate that premature infants with GA ranging from 24 to 32 weeks had a higher level of IL-8 (p = 0.029), but not level of IL-10 (p = 0.109), in the BAL obtained during the first intubation compared to premature infants with GA ranging from 33 to 37 weeks. The administration of exogenous surfactant did not influence the profiles of IL-8 and IL-10, as compared to those in-patients without treatment. Levels of IL-8 were correlated with IL-10 levels (r = 0.613, p = 0.007) in BAL fluid samples obtained on the day of intubation. The level of IL-8, but not IL-10, was significantly correlated with the duration of intubation. IL-8 and IL-10 levels in BAL fluid samples collected on the day of intubation were correlated with the development of chronic lung disease (CLD). The results suggest that extreme prematurity tends to have increased IL-8 and IL-10 levels in BAL fluid compared to premature infants with older GA, and that these increased levels are associated with the development of CLD.

Hemoglobin (Hb) S Antilles is a naturally occurring form of sickling human Hb but causes a more severe phenotype than Hb S. Two homozygous viable Hb S Antilles transgene insertions from Tg58Ru and Tg98Ru mice were bred into MHOAH mice that express high oxygen affinity (P50 approximately 24.5 mm Hg) rather than normal (P50 approximately 40 mm Hg) mouse Hbs. The rationale was that the high oxygen affinity MHOAH Hb, the lower oxygen affinity of Hb S Antilles than Hb S (P50 approximately 40 v 26.5 mm Hg), and the lower solubility of deoxygenated Hb S Antilles than Hb S (approximately 11 v 18 g/dL) would favor deoxygenation and polymerization of human Hb S Antilles in MHOAH mouse red blood cells (RBCs). The Tg58 x Tg98 mice produced have a high and balanced expression (approximately 50% each) of h alpha and h beta(S Antilles) globins, 25% to 35% of their RBCs are misshapen in vivo, and in vitro deoxygenation of their blood induces 30% to 50% of the RBCs to form classical looking, elongated sickle cells with pointed ends. Tg58 x Tg98 mice exhibit reticulocytosis, an elevated white blood cell count and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.

Six Han, 6 Uighur and 6 Kazak healthy volunteers took orally a single dose of 1000 mg josamycin tablets. The concentrations of the drug in serum were detected with bioassay method. The results showed that the pharmacokinetic courses were very similar among these three ethnic groups and fitted to a one-compartment open model. The results in these three groups showed no significant difference.