If we can add how to avoid medical dispute into clinical education,it must be very helpful to young doctors in their medical work after graduation.The article analyzed the cause of medical dispute,and proposed how to enhance the education of medical dispute avoiding,and prove a efficient way to improve clinical education.

Objective To evaluate clinical value of denaturing high performance liquid chromatography (DHPLC) used in detecting transforming growth factor beta receptor 3 (TGFBR-3) exons 11 and 12 polymorphism in women with idiopathic premature ovarian failure (POF).Methods From Feb.2009 to Dec.2011,110 patients with idiopathic POF undergoing treatment at Shenzhen Maternal & Child Health Institute affiliated to Southern Medical University were enrolled as POF group in this study.In the mean time,110 women under 40 years old with normal hormonal level and menstrual cycles as control group.The exons 11 and 12 of TGFBR-3 gene polymorphism were screened by using DHPLC,and results of DNA sequencing was as golden standard.Some related indexes were calculated,such as sensitivity,specificity,false negative value,false positive value,Youden index,positive predictive value,and negative predictive value.At the same time,20％ of the tested specimens were chosen randomly and detected by DHPLC again.The value of Kappa index were calculated by comparing the results between the first and second DHPLC analysis.Results The exon 11 of TGFBR-3 were not identified gene polymorphism and two nucleotide polymorphisms were identified in exon 12.For 2022 T/C polymorphism,the frequencies of CC with 0.9％ (1/110),TC with 22.7％ (25/110),TT with 76.4％ (84/110),Cwith12.3％ (27/220) and T with 87.7％ (193/220) in POF group were significantly different from CC with 0,TC with 9.1％ (10/110)and TT with 90.9％ (100/110),C with 4.5％ (10/220) and T with 95.5％ (210/220) in control group (all P ＜ 0.05).Allelic and genotypic frequencies of 2161-75 C/T were not differed significantly between the two groups (all P ＞ 0.05).As DNA sequencing as golden standard,DHPLC showed that the sensitivity was 100％,specificity was 97.9％,Youden index was 97.9％,positive predictive value was 96.3％,negative predictive value was 100％,and Kappa index was 0.888 (P ＜ 0.05).Conclusion DHPLC analysis is higher validity,reliability and practicability method in detecting TGFBR-3 polymorphism in idiopathic premature ovarian failure.

BACKGROUND: Diphosphonate has a predominant therapeutic effect in the prevention and treatment of postmenopausal osteoporosis. Ibandronate, as a new-type diphosphonate preparation, is gradually becoming a study hotspot.OBJECTIVE: This study is to investigate the efficiency of ibandronate in interfering postmenopausal osteoposis by observing bone mass loss related indexes in ovariectomized rats, and made a comparison with nilestriol.DESIGN: A completely randomized grouping, and controlled animal experiment.SETTING: Study Room for Bone metabolism, Fudan University Medical College.MATERIALS: Forty SD female rats, aged 10-12 months, were involved in this study. Ibandronate was provided by the State Key Laboratory of Jiangsu Institute of Atomic Medicine. Nilestriol was produced in the Shanghai 12th Pharmaceutical Factory.METHODS: This experiment was carried out in the Study Room for Bone Metabolism, Institute of Radiation Medicine,Shanghai Medical University between August 1996 and June 1998. The rats were divided into 4 groups by a lot, 10 rats in each: sham-operation group, ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group. In the sham-operation group, only small pieces of adipose tissue around the ovary were resected from the rats.Three months after operation, each rat was intragastrically administrated with 1 mL normal saline; In the ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group, each rat was subjected to bilateral ovariectomy, and 3 months later, they were intragastrically administrated with normal saline, ibandronate water solution [0.5 mg/( kg·d)] and nilestriol suspension [1 mg/(kg· time)] respectively. Each rat in the latter three groups was administrated for 90 days, twice in the first week, and then once a week.MAIN OUTCOME MEASURES: Left femur was taken out, and its dry weight and ash weight were measured. Calcium content of bone was determined with an atomic absorption spectrophotometer, bone density of the whole body with a bone density apparatus, the bone density at the juncture of 1/2 right femoral bone length with a single photon bone density apparatus, and femoral anti-bending force was determined with a universal testing machine. Alkaline phosphatase were determined by dynamical method with an automatic biochemistry analyzer, urine calcium by EDTA titration method, urine creatinine by picric kinetic method, and urinary hydroxyproline by modified proline assay.Trabecular area was calculated.RESULTS: Forty rats were involved in the final analysis. ① Bone dry weight, bone ash weight and bone calcium content in the ovariectomized group were significantly lower than those in the other 3 groups, respectively (t =13.58-52.98, P ＜0.05). ② Femoral bone density and bone density of the whole body of rats in the ovariectomized group were significantly lower than those in the other 3 groups (t =3.31-5.61, P＜0.05), while anti-bending force was close between ovariectomized group and the other 3 groups (P＞0.05). ③ The ratio of urine calcium to urine creatinine was significantly lower in the ovariectomized+ibandronate group and ovariectomized +nilestriol group than in the ovariectomized group (t =4.04, 3.30, P＜0.05). No significant difference in the alkaline phosphatase and ratio of urinary hydroxyproline to urinary creatinine existed among the groups (P ＞ 0.05). ④Trabecular area of vertebrae in the ovariectomized group was significantly smaller than that in the other 3 groups (t =2.22,2.41,3.45,P ＜ 0.05), while the trabecular area of tibia in the ovariectomized group was only smaller than that in the ovariectomized +nilestriol group (t =2.45, P＜ 0.05).CONCLUSION: Osteoporosis apPears obviously in the SD rats 3 months after ovariectomy. Ibandronate has obviously inhibitory effects on the bone mass loss of rats with postmenopausal osteoposis, and it is equivalent to nilestriol in inhibitory effect.

Objective To assess the influence of length of the alanine tract of forkhead box E1 (FOXE1) gene on genetic susceptibility to idiopathic premature ovarian failure (POF). Methods Totally 110 patients with idiopathic POF were recruited between February 2009 and December 2012 at the Affiliated Shenzhen City Maternity and Child Healthcare Hospital of Southern Medical University. Controls (n=110) were individuals with normal menstrual cycles, normal FSH concentrations. The polyalanine tract and flanking sequence of FOXE1 were screened using the multiplex ligation-dependent probe amplification (MLPA) technique and direct sequence technique. Results The most frequent of FOXE1 polyalanine stretch length was 14 residues in both groups. The length of FOXE1 polyalanine reported in this study varied from 12 to 16 alanines, and three variants of FOXE1-polyalanine length, containing 12, 14, or 16 alanine residues, and 5 different genotypes were identified. The most common genotypes were 14/14 homozygote, occurring with the frequency of 81.8% (90/110) in the POF group, while 96.4% (106/110) in control subjects, respectively. The incidence of 14/14 genotypes of FOXE1-polyalanine was significantly lower in patients with POF (χ2=119.730, P=0.001) in comparison to the controls. There were significantly higher frequencies of the 16/16 genotypes in cases with POF [10.0% (11/110) versus 0; χ2=3.403, P=0.001], as compared with the controls. The FOXE1 14 alanine allele was significantly less common in the POF patient group than the controls [84.5% (186/220) versus 98.2% (216/220); χ2=25.923, P=0.001]. The FOXE1 16 alanine allele was significantly more common in the POF patient group than the controls [12.7% (28/220) versus 1.8% (4/220); χ2=19.412, P=0.001]. Conclusions The polymorphism of the polyalanine tract of FOXE1 gene have a certain relevance for the genetic aetiology of idiopathic POF.

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ²=54.79, P<0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95%CI) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection (OR (95%CI): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 (OR (95%CI): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

Objective To investigate the regulation of SIRT1 on ovarian granulosa cell in women with poor ovarian response.Methods A total of 60 women who underwent IVF/ICSI-ET were included in this study,30 women in poor ovarian response(POR)group and 30 women in normal ovarian response(NOR)group.The granulosa cells in follicular fluid were isolated and purified by density gradient centrifugation.The granulosa cells of POR group were treated with SIRT1 agonist resveratrol(RESV)or inhibitor EX527,respectively,and the control group was granulosa cells treated without drugs.mRNA levels of SIRT1 and key enzymes of steroid hormone synthesis(StAR,CYP19,CYP17)in granulosa cells were detected by qPCR.The levels of SIRT1,steroid hormone synthesis key enzymes protein and apoptosis-related protein(Bcl-2,Caspase-3)in granulosa cells were detected by Western blot.The apoptosis rate of granulosa cells was detected by TUNEL method.Determination of estradiol in granulosa cell culture medium by chemiluminescence.Results The mRNA and protein levels of SIRT1 in granulosa cells in POR group were lower than those in NOR group(P = 0.003,P<0.001).RESV up-regulated SIRT1 mRNA and protein levels(P<0.001),up-regulated mRNA and protein levels of steroid hormone synthesis key enzyme(P<0.05).EX527 down-regulated SIRT1 mRNA and protein levels(P = 0.023,0.001),down-regulated mRNA and protein levels of steroid hormone synthesis key enzymes(P<0.05).After RESV treatment,the apoptosis rate of granulosa cells was decreased(P<0.001),the Bcl-2 protein level was increased(P<0.001),and the Caspase-3 protein level was decreased(P<0.001).After EX527 treatment,the apoptosis rate of granulosa cells was increased(P<0.001),the Bcl-2 protein level was decreased(P = 0.003),and the Caspase-3 protein level was increased(P<0.001).Conclusion The SIRT1 level in granulosa cells of POR women was lower than that of NOR women.RESV up-regulated SIRT1 expression in granulosa cells.SIRT1 inhibited granulosa cell apoptosis,increased the level of steroid hormone synthesis key enzyme,and promoted estradiol synthesis in granulosa cell.Therefore,SIRT1 activators such as RESV may be a therapeutic agent to improve ovarian reactivity and increase the number of oocytes obtained in women with POR.

Objective: To analyze the epidemiological genotype features of human papillomavirus (HPV) in cervical infection and their risks for cervical precancers among women in Shenzhen area. Methods: A total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology (LBC), colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia (CIN) 2 and above were estimated. Results: The HPV infection rate in Shenzhen area was 15.9% (432/2 717). The most common HPV genotype was HPV52 (22.9%), followed by HPV16 (12.7%), HPV53 (10.0%), HPV51 (8.6%) and HPV58 (8.1%). Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity (57.1% vs. 42.9%, P<0.05) and an analogous specificity (87.3% vs. 86.9%, P>0.05) in predicting CIN2+ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion (LSIL) positive tested by LBC in predicting CIN2+ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance (ASC-US) positive tested by LBC alone (P<0.05). The specificities of these two methods mentioned above in predicting CIN2+ were 83.5% and 89.2%, respectively, without statistical difference (P>0.05). Conclusions Women infected by HPV have distinct risks for CIN2+ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL+ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.