Objective To explore the technology frontiers for neuroblastoma treatment from the perspective of patent citation network. Methods Through patent analysis for neuroblastoma treatment, highly cited patents and highly cited papers in the citation network were taken as the research objects. The title and abstract of the citing patents were analyzed by text clustering to identify the technology frontiers. Through social network analysis, the core patents were identified from the indices of degree centrality, betweenness centrality, closeness centrality, and eigenvector centrality. Results A total of 6240 patent applications for neuroblastoma treatment were found, including 71304 patent citations and 88698 journal-article citations. Four technology frontiers were identified based on patent citation network, namely, drug target, drug design, tumor-indication expansion, and gene-expression regulation. Three technology frontiers were identified based on journal-article citation network. They were drug target, drug design, and tumor-indication expansion. Conclusion The development of technology for neuroblastoma treatment continues to be active. Drug target and drug design are the most important technology frontiers. This study could provide certain reference for neuroblastoma treatment from the perspective of information science.

Objective Explore the value of anti-Müllerian hormone(AMH)in predicting pregnant outcomes of polycystic ovary syndrome (PCOS) patients undergone assisted reproductive technology. Methods The study totally recruited 1697 patients who underwent the first in vitro fertilization (IVF) or intracytoplasmic sperm injection(ICSI)cycle in Sun Yat-sen Memorial Hospital from the January 2014 to December 2015. The patients were divided into two groups based on the age<35(n=758)and≥35 years old (n=939), compare the basic data and pregnant outcomes of controlled ovarian hyerstimulation. Spearman correlation method was conducted to analyze the relations between AMH and clinical outcomes. The logistic regression method and partial correlation analysis were used to judge the main factors which determine pregnancy outcomes by controlled the confounding factors. The receiver operating characteristic curve (ROC)was used to evaluate the predictive sensitivity and specificity of AMH. Results In the group of PCOS patient younger than 35 years, AMH were correlated with the number of antral follicles(r=0.388)and retrieved oocytes (r=0.235). When the effect of total dosage and starting dosage of gonadotropin were controlled, AMH was still significantly associated with the number of retrieved oocytes(P<0.05). AMH had no predictive value for the clinical pregnancy of PCOS patient younger than 35 years (area under ROC curve=0.481, P=0.768). In the group of PCOS patient≥35 years old, AMH were correlated with the number of antral follicles (r=0.450), retrieved oocytes (r=0.399), available embryo (r=0.336) and high quality embryo(r=0.235). When the effect of total dosage and starting dosage of gonadotropin were controlled, the correlations were still significant between those indexes(all P<0.05). AMH had no predictive value for the clinical pregnancy of PCOS patient≥35 years old(area under ROC curve=0.535, P=0.560). However, the clinical pregnancy rate of the group of PCOS patient≥35 years old was slightly higher than the control group (P=0.062). Conclusions AMH has no predictive value for the pregnancy outcome of PCOS patient. The pregnancy rate of PCOS patient≥35 years old is slightly higher than the younger group, because the PCOS patient may have better ovarian reserve.

Objective To investigate the efficacy and safety of intravesical instillation with Sufuning (SFN) lotion for prevention of postoperative recurrence of bladder cancer. Methods A total of 240 bladder cancer patients who were diagnosed as bladder cancer and accepted trans-urethral resection of bladder tumor from January 2010 to June 2016 in Shanxi Provincial Cancer Hospital were randomly divided into the experimental group (120 cases) and the control group (120 cases) according to the envelope method. The patients in the experimental group were treated with SFN lotion for immediate intravesical instillation(250 mg for once), and the patients in the control group were treated with pirarubicin (THP) for immediate intravesical instillation (30 mg for once). The patients of two groups were treated with intravesical chemotherapy once a week for 8 times, and the chemotherapy was performed once a month for 1 year. The recurrence rate, progression-free survival (PFS) rate, overall survival (OS) rate and recent side effects were compared between the two groups. Results The patients were followed up for 6 to 60 months. The median follow-up time was 36.5 months.In the experimental group,6 patients were lost and 8 patients were lost in the control group.The experimental group, the total recurrence rate was 26.3 % (30/114). The control group, the overall recurrence rate was 25.0 % (28/112) (χ2= 0.142, P = 0.781). Five years of PFS rate in the experimental group and the control group was 73.7 % (84/114) and 75.0 % (84/112) respectively, and there was no significant difference between the two groups (χ2= 2.011, P= 0.615). Five years of OS rate in the experimental group and the control group was 95.6 % and 92.9 % respectively, and there was no significant difference between the two groups (χ 2= 1.611, P= 0.425). The major side effects included chemical cystitis and hematuria. The incidence of chemical cystitis and hematuria in the experimental group was significantly lower than that in the control group(χ2=5.991,P=0.018;χ2=4.925,P=0.036).There was a statistically significant difference of the hematological side effects (blood routine changes) between the two groups (χ 2= 4.891, P= 0.032). Conclusion It is safe and effective for intravesical instillation of SFN lotion to prevent the recurrence of bladder cancer.

[Objective]To evaluate the terminal hair growth of different body positions among in pregnant women ,analyze the contribution of each area to the diagnosis to hirsutism ,to improve the mFG scoring system.[Method]Pregnant women aged 20~41 years,with normal range of total testosterone levels and non-hirsute were recruited at their prenatal care in Sun Yat-sen Memorial Hospital,Sun Yat-sen University. They were followed up before pregnancy,at the 5th and the 9th week,the 10th and the 14th week, the 15th and the 20th week,the 21th and the 24th week of gestation. Then 72 more cases of pregnant women were recruited and followed up at 15~24th week. At each time of followed up,their total testosterone(TT)levels was examined by liquid chromatography tandem mass spectrometry(LC/MS-MS)and terminal hair growth were assessed by mFG score. Significant difference procedure least(LSD) analysis of variance was used to compare the levels of testosterone and mFG score in different gestational weeks. Receiver operating characteristics(ROC)analysis and logistics analysis were conducted to evaluate the contributory strength of hair growth in each body position for the diagnosis of hirsutism. The scores in the body area which made a significant contribution to the total were summed up and termed the simplified mFG score(sFG score). Following,the sFG scores were subjected to ROC analysis to determine the thresh-old that would maximize both the sensitivity and specificity of the measure to accurately distinguish hirsute from non-hirsute patients.[Results]Among the forty three pregnant women who were followed-up from before pregnancy to 24th week,the mean±SD for TT was (1.09 ± 0.59)nmol/L before pregnancy,and(1.13 ± 0.40),(1.28 ± 0.38),(1.83 ± 0.63),(1.82 ± 0.52)nmol/L for 5~ 9th,10~14th,15~20th week,and the mFG score was 1.65 ± 0.60,2.30 ± 0.45,3.60 ± 0.68,4.20 ± 0.41 and 4.40 ± 0.77,respectively. The order of the facial and body sites presented with new terminal hair growth was upper abdomen,lower abdomen,lower back,up-per lip,thighs,upper back,chest,upper arm,and chin,in sequence. After analyzing 115 cases(including the 72 cases recruited later),ROC analysis showed that the diagnostic value of different sites for hirsutism(mFG≥5):upper lip>lower back>thighs>lower abdomen>upper arm>upper back>chest/upper abdomen. Four sites among them ,namely upper lip ,lower back ,thighs and lower abdomen had the best diagnostic value,and the AUC for ROC were 0.779,0.728,0.675,and 0.626,respectively. Both ROC and logistic analysis indicated that he most significant body areas in defining hirsutism(defined as an mFG score≥5)were the upper lip, lower back,thighs,and lower abdomen. Using a cut-off value of 3,the combination of the four areas has the best sensitivity and specificity in distinguishing hirsute from non-hirsute women. [Conclusion]The study suggested that the mFG score increased as pregnancy progressed before the 24 weeks of gestation. The subset of upper lip,lower back,thighs and lower abdomen may be a reli-able simplification of mFG system for the evaluation of excess hair growth. The cut-off value was of≥3.

Objective To compare the difference of serum adiponectin levels between polycystic ovary syndrome (PCOS) patients and age, boby mass index (BMI) and insulin-resistance index matched controls, and explore its influence factors.Methods Case-control study, involving 97 women with PCOS and 116 age, BMI, fasting plasma glucose and insulin levels, homeostasis model assessment-insulin resistance index (HOMA-IR) matched controls.Hormone profiles, and serum adiponectin levels were measured and compared.Hormone profiles and serum adiponectin levels were compared among the four PCOS phenotypes.Multiple regression analysis was used to evaluate the factors affecting serum adiponectin levels.Results (1) Serum adiponectin level was significantly lower in PCOS group [(21 ± 16) mg/L] than controls [(25± 13) mg/L, P=0.038], and the same result in stratified analysis on weight height ratio (WHR, ≥0.8 and ＜0.8).(2) There was statistical differences in testosterone among different four PCOS phenotypes (P=0.001), there were no statistical differences in FSH, LH, WHR and serum adiponectin levels among four PCOS phenotypes (P＞0.05).(3) WHR and PCOS status were independent determinants of serum adiponectin levels (P＜0.05).Conclusions Low serum adiponectin levels in the women with PCOS is correlated with PCOS per se, independent of insulin resistance and obese.This fact supports the further study of the effect of adiponection in the pathophysiology of PCOS and its log-term impact.

OBJECTIVETo assess the association of rs13405728 polymorphism of luteinizing hormone receptor (LHR) gene with slow ovarian response during assisted reproductive technology (ART).

METHODSTwo hundred and thirty-six women were enrolled and grouped according to their genotypes. The rs13405728 polymorphism was genotyped by DNA sequencing.

RESULTSNo signifiicant difference was found in antral follicle count and anti-Mullerian hormone between the three genotypes (P>0.05). The incidence of slow response in genotype GG was lower than in the other two genotypes (P<0.05). There was no significant difference in the amount of follicle stimulating hormone required, the number of follicles ≥14 mm on human chorionic gonadotrophin day, oocytes, mature oocytes, available embryos, and the clinical pregnancy rate among the three genotypes (P>0.05). There was an independent correlation between slow ovarian response with the genotypes of rs13405728, the initial dose of gonadotropin, and the dose of luteinizing hormone required (P<0.05).

CONCLUSIONRs13405728 of the LHR gene may be associated with slow ovarian response in ART. Various mechanisms may be involved in the poor response and slow response.

Adult ; Female ; Fertilization in Vitro ; methods ; Gene Frequency ; Genotype ; Humans ; Logistic Models ; Ovarian Reserve ; genetics ; Ovulation Induction ; methods ; Polymorphism, Single Nucleotide ; Receptors, LH ; genetics ; Reproductive Techniques, Assisted ; Sequence Analysis, DNA ; methods

Objective To evaluate the effect of the difficult embryo transfer on the clinical pregnancy outcome of in vitro fertili-zation-embryo transfer(IVF-ET) .Methods There were 209 fresh cycles of difficultly transferring and 2 489 fresh cycles of easily embryo transferring between January 2011 and December 2012 .The clinical outcome was compared .Results There were statistical-ly significant differences in the catheter blood staining rates (51 .20% vs 27 .68% ,P< 0 .05) ,implantation rate(31 .14% vs 35 . 54% ,P<0 .05) ,and clinical pregnancy rate (46 .41% vs 55 .56% ,P<0 .05)between the two groups .There was no significant difference in the rates of ectopic pregnancy and miscarriage between the two groups (P>0 .05) .Conclusion Difficulty ET will in-fluence the clinical pregnancy .Therefore ,all efforts should be made to avoid the difficult transfer in order to increase the pregnant rate .

A total of 1 107 Chinese women were retrospectively investigated for the effects of overweight and underweight on ovarian stimulation, as well as the outcomes of in vitro fertilization and embryo transfer (IVF-ET)treatment. It showed that overweight women required more ampoules of gonadotrophin [ (36. 87 ±11. 18 vs 33.57±10.96)/ampoule,P<0.01]and had lower peak of estradiol concentration [ (1 846.6±1 390.3 vs 2 337.2± 1 490.6)pg/ml,P<0.01].increased cycle cancellation due to insufficient follicle development(6. 5% vs 2. 8% , P<0.05) ,and a higher miscarriage rate( 10.5% vs 5.4% ,P<0.05)compared with normal weight women. But no differences were found in clinical pregnancy and live birth rates. Compared with normal weight women, underweight women showed no differences in ovarian stimulation and IVF outcome.

Objective This study was designed to investigate the correlationship between plasma metastin and pathogenesis of adolescent women with polycystic ovary syndrome(PCOS).MethodsFrom Jan 2006 to Jun.2006.42 PCOS patients including 19 adolescent women and 23 adults with syndrome were treated in Second Affiliated Hospital of Sun Yat-Sen University.According to the range of age,those patients were divided into 19 cases in adolascent group(≤19 years)and 23 cases in aduh group(＞19 years).Meanwhile,20 adolescent women were matched as controls.Blood samples were collected between day 1 and day 5 of a spontaneous bleeding episode in the PCOS groups and a menstrual cycle of the controls.The Jevels of luteinizing hormone(LH)，follicle-stimulating hormone(FSH)，testosterone(T)，free T(FT)，dehydroepiandrosterone sulfate(DHEAS)，sex hormone-binding globulin(SHBG)，insulin，glucose，and metastin were detected from day 1 to day 5 of spontaneous bleeding or withdrawal bleeding by progesterone.On the next day,oral glucose tolerance test(75 g)and insulin release test were performed on those above patients and controls.The area under carve(AUC),the ratio of fasting blood glucose to insulin(GIR)and homeostasis model assessment insulin resistance jndex ( HOMA-IR)were calculated.Results(1)The level of hormone:the level of LH was in(12±7)U/L in adult group and(12±8)U/L in adolescent PCOS group，which were significantly higher than(6±4)U/L in controls(P＜0.05).The level of FT was(2.3±1.2)pmol/L in adult group，which was significantly higher than(1.3±0.8)pmol/L in adolescent group and(1.1±0.5)pmol/L in control roup(P＜0.05).It was observed that the level of(3.1±2.7)μmol/L in adolescent group was significantly lower than(6.3±2.7)μmol/L in control group(P＜0.05).Meanwhile,the level of FAI of 5.6±4.1 in adult group was significantly higher than 3.0±1.3 in control group(P＜0.05).No significant difference in FSH，T and SHBG levels among three groups were observed (P＞0.05).(2)Metastin and metabolism:Both the levels of fasting blood insulin,2-hour insulin and AUC of insulin were(13±7)mU/L，(88±59)mU/L and(133±80)mU·L-1·min-1 in adolescent group，which were significantly higher than(7±3)mU/L，(57±29)mU/L and(82±34)mU·L-1·min-1 in control group.The fasting blood insulin of(13±7)mU/L in adolescent group was significantly higher than (9±5)mU/L in adult group.The level of fasting blood glucose and 2-hour glucose were(5.01±0.44)mmol/L and(6.48±1.16)mmol/L in adult group，which were significantly higher than(4.68±0.29)mmol/L and(5.44±0.83)mmol/L in control group and(4.67±0.30)mmol/L and(5.93±1.44)mmol/L in adolescent group.The glucose AUC of(9.99±1.85)mmol·L-1·min-1 in adult group was significantly higher than(8.42±1.53)mmol·L-1·min-1 in control group(P＜0.05).HOMA-IR of 2.6±2.0 in adolescent group was significantly higher than 1.4±0.7 in control group.GIR of 10±8 in adolescent group was significantly lower than 16±10 in control group(P＜0.05).The metastin level of (0.25±0.19)pmol/L in adolescent group and(0.29±0.29)pmol/L in adult group were all significantly higher than(0.18±0.23)pmol/L in control group(PPh glucose were observed(r=0.256，0.286 and 0.267.P=0.044.0.025 and 0.043).Conclusions The expression of metastin in adolescent PCOS women was significantly higher that of normal adolescent women The increased level of metastin might be associated with pathogenesis of adolescent women with PCOS.

Objective To investigate the effect of anti-Mlllerian hormone (AMH) on hormone secretion and P450 aromatase mRNA expression from cultured human luteinized granulosa cells. Methods Human luteinized granulose cells were derived from 10 patients treated by in vitro fertilization-embryo transplantation (IVF-ET) in the Second Affiliated Hospital of Sun Yat-sen University from June to December 2006. Granulose cells were divided into group A, B, C, D, E depending on different concentration of AMH,testosterone group and blank group. 1×10-7moL/L testosterone and 1,5,10,20,50 μg/L AMH were added into the culture medium of group A,B,C,D and E. 1×10-7mol/L testosterone was added into the culture medium of testosterone group while no other ingredient was added into the medium of blank group. Estrogen levels in supernates were measured at 24,48,72 hours after cell incubation. RT-PCR was performed to detect the P450 aromatase mRNA expression in group B, C, D, E and testosterone group at 72 hours after cell incubation. Results (1) Estrogen levels in supernates of granulose cell culture at 24,48,72 hours were (8.529±0.381)×104, (10.977±0.436)×104, (13.309±0.506)×104 pmol/L in group A, (7.027±0.276)×104, (9.167±0.300)×104, (10.794±0.555)×104 pmol/L in group B, (6.039±0.226)×104,(7.585±0.548)×104, (8.797±0.518)×104 pmol/L in group C, (5.118±0.460)×104, (5.716±0.496)×104, (6.205±0.667)×104 pmol/L in group D, (4.932±0.148)×104, (5.323±0.184)×104,(5.629±0.212)×104 pmol/L in group E. When compared with blank group [(0.001±0.001)×104,(0.006±0.003)×104, (0.029±0.011)×104 pmol/L], the statistical differences were observed in group A,B,C,D,E(P<0.01) ; when compared with testosterone group [ (8.418±0.569)×104, (10.841±0.689)×104, (13.301±0.637)×104 pmol/L], the statistical differences were observed in group B,C,D and E(P<0.01) ; statistical differences were also observed in group C, D and E when compared with group B, and also group D and E when compared with group C(P<0.01). No significant difference was observed between group D and E (P>0.05). In group A, B, C, D, E and testosterone group, the estrogen levels at 24 hours after cell culture were significantly lower than those at 48 and 72 hours (P<0.01) ; statistical difference was observed between estrogen levels at 48 and 72 hours(P<0.01). No significant difference was observed among 24,48 and 72 hours in blank group (P>0.05). (2) Relative ratios of intensity of P450 aromatase/β-actin at72 hours of cell culture in group B,C,D and E were 0.6148±0.0046, 0.5156±0.0012, 0.4698±0.0027 and 0.4282±0.0017, respectively, which were statistically lower than that in testosterone group (0.8224±0.0021, P<0.01) ;statistical differences were also observed in group C, D and E when compared with group B, and also group D and E when compared with group C(P<0.01). No significant difference was observed between group D and E (P>0.05). Conclusion It is suggested that AMH might affect estrogen synthesis by inhibiting P450 aromatose activity so that lead to hyperandrogenism microenvironment in local ovary.