Objective To investigate the quality of life and sexual function of cervical cancer patients following radical hysterectomy (RH) and vaginal extension.Methods Case-control and questionnaire-based method was employed in this study.Thirty-one patients of early-stage (Ⅰ b1-Ⅰ b2) cervical cancer who had undergone vaginal extension following classic RH in Peking Union Medical College Hospital from December 2008 to September 2012 were included in study group,while 28 patients with matching factors and RH only during the same period were allocated to control group.There was no significant difference between two groups in terms of clinical and demographic variables including age at diagnosis,tumor stage and follow-up time (P＞0.05).Patients were assessed retrospectively by validated selfreported questionnaires the European Organization for Research and Treatment of Cancer Cervix Cancer Module Questionnaire (EORTC QLQ-CX24) mainly for quality of life and sexual function for cervical cancer patients; the Sexual Function and Vaginal Changes Questionnaire (SVQ) further investigates sexual function and vaginal changes of patients with gynecologic malignancy at least 6 months after treatment.Results Vaginal length acquired by pelvic examination by gynecologic oncologists during follow-up visits was (10.0±1.3) cm and (5.9± 1.0) cm in study group and control group respectively (P=0.000).Sixty-eight percent (21/31) of cases in study group and 64％ (18/28) of cases in control group had resumed sexual activity at the time of interview,and the time interval between treatment and regular sexual activity was mean 6 months (range 3-20 months) and mean 5 months (range 1-12 months) in study and control group respectively,in which there was not statistical significance (P＞0.05).No difference was observed regarding pelvic floor symptoms (P＞0.05) while difficulty emptying bladder,incomplete emptying and constipation were most commonly reported.Both group presented with hypoactive sexual desire disorder [88％ (52/59)],orgasm dysfunction [72％(28/39)] and low enjoyment or relaxation after sex [51％(20/39)],which was not statistically significant (P＞0.05).Reduced vagina size and shorter vagina was more prominent in control group (12/18) than that in study group [19％ (4/21)] with statistical significance (P＜0.05),while no difference in sexual desire,vaginal lubrication,dyspareunia and sexual enjoyment (P＞0.05).Conclusions Patients with peritoneovaginoplasty following RH had much longer vagina and less self-perceived short vagina.Vaginal extension following RH does not worsen the pelvic floor symptoms.

Objective To investigate the mechanism of mastoparan-1 (MP-1) antagonizing lipopolysaecharide (LPS) in vitro. Methods The affinity of MP-1 for lipid A was assayed by biosensor, and the neutralization of MP-1 on LPS (2 μg/L) was detected by kinetic turbidimetric limulus test. After exposing fluorescin isothiecyanate (FITC) labeled LPS (FITC-LPS) to MP-1 at different concentrations (5, 10, 20, 40 μmol/L), the binding of FITC-LPS to murine RAW264.7 cells was analyzed by laser scanning confocal microscopy. The influence of MP-1 on TLR4 expression in RAW264.7 cells stimulated by LPS (100 μg/L) was detected by immunoeytochemieal staining. The expressions of TLR4, TNF-α and IL-6 at the gene and protein level were detected by RT-PCR and ELISA after exposing LPS (100 μg/ L) stimulated RAW264.7 cells to MP-1 at different concentrations. The effect of MP-1 on the viability of RAW264.7 cells was detected by MTT assay. Results MP-1 had high affinity to lipid A and could neutralize LPS. MP-1 at 10 μmol/L significantly inhibited not only binding of FITC-LPS to RAW264.7 (P < 0.05), but also protein and gene expressions of TLR4, TNF-α and IL-6 in LPS stimulated RAW264.7 cells in a dose-dependent manner (P < 0.05). No toxic effect of MP-1 on the viability of RAW264.7 cells was found (P > 0.05). Conclusions MP-1 inhibits cell viability mediated by LPS, which may be related to its neutralization of LPS and inhibition of binding of LPS to RAW264.7 cell membrane receptors.

Objective To compare the effect between intra-arterial and intra-venous neoadjuvant chemotherapy(NACT)in stage Ⅰb2-Ⅱ b cervical carcinoma.Methods A retrospective analysis Was done on 52 cases of intra-venous NACT and 95 eases of intm-arterial NACT for stage Ⅰ b2-Ⅱ b cervical carcinoma treatad in Peking Union Medical College Hospital from 1999.ResulIs The response rate of intraveHous NACT and intra-arterial NACT was 88%(46/52)and 79%(75/95).and the operative rate after NACT Was 81%(42/52)and 72%(68/95)respectively(P>0.05).There were no significant differences in surgery time,blood loss and pest-operative morbidity between these two groups.Pathological parametrial positive rate after NACT in arterial group(6%)Was significantly lower than that of venous group (50%,P>0.05).The venous group had very similar recurrence rates(13%vs 17%)and death rates (9%VS 12%)when compared with the arterial group(P>0.05).Conclusions The intra-arterial and intra-venous NACT for stage Ⅰ b2-Ⅱb cervical carcinoma show similar response rate.operative rate and surgical difficulties.Arterial NACT shows a better effect on parametrial infiltration.

Objective To evaluate the prognosis and fertility outcomes of patients with early stage of cervical cancer treated by vaginal radical trachelectomy ( VRT ) in combination with laparoscopic pelvic lymphadenectomy.Methods The surgical data , disease recurrences and fertility outcomes were analyzed retrospectively for 51 patients who received VRT in Peking Union Medical College Hospital from Dec.2003 to Nov.2013.Results Forty-eight patients succeeded in preserving fertility.The median age was 29 years.International Federation of Gynecology and Obstetrics ( FIGO ) stage: 5 cases Ⅰa1 with lymph vascular space invasion (LVSI),4 cases Ⅰa2 and 39 cases in stage Ⅰb1.Tumor size: 20 cases with no visible lesion, 20 cases with tumor size ≤2 cm, 8 cases with tumor size >2 cm.Histological type:42 cases with squamous carcinoma , 6 cases with adenocarcinoma or adeno-squamous carcinoma.The mean excised cervical length and parametrial width was ( 2.6 ±0.6 ) cm and ( 1.9 ±0.5 ) cm, respectively.Six recurrences ( 12%) were observed after following up for a mean duration of ( 35 ±21 ) months.The recurrent rate in patients with tumor size >2 cm was 3/8, which was significantly higher than that of the
patients with tumor size ≤2 cm (8%, 3/40;P<0.01).Of the 35 patients who desired to conceive after the surgery, 13 women had 17 pregnancies and the pregnant rate was 37% (13/35).Nine women obtained 10 healthy live birth babies.The fertility rate was 26%( 9/35 ).Conclusions VRT in combination with laparoscopic pelvic lymphadenectomy could preserve the fertility of patients with early stage of cervical cancer with acceptable oncologic and fertility outcomes.Tumor size ≤2 cm should be emphasized as the indication of VRT in considering of the higher recurrent rate in patients with tumor size >2 cm.

Objective To assess the correlation of promoter methylation of DAPK1,RAR-β and MGMT with cervical lesions from cytology to histology,and to reveal the clinical value of DNA methylation in diagnosis of cervical intraepithelial neoplasia (CIN).Methods A total of 103 random-selected cervical samples were collected from residual liquid-based cytology specimens after clinical use in cytopathological diagnosis in outpatient clinic of obstetrics and gynecology,Peking Union Medical Collage Hospital from March 2010 to October 2010.Informed consent was obtained from each woman before the initiation of the study.The methylation seusitive-high resolution melt (MS-HRM) assay was used to evaluate promoter methylation of three genes ( DAPKI,RAR-β and MGMT) in 103 biopsy-confirmed liquid-based cervical cytology samples.Methylation levels and high-risk HPV DNA loading ( HC Ⅱ values) were analyzed in relation to both cytological and histological diagnosis.Results The methylation level of all three genes showed significant difference among the different cytological groups ( P =0.000,0.011 and 0.002,respectively).The methylation level of DAPK1 and RAR-β showed significant difference among the different histological groups ( P =0.000 and 0.021 ),while there was no significant difference for MGMT.DAPK1 methylation levels was 1.47％ in the CIN Ⅱ/high-grade precancerous lesions group,and 20.98％ in the normal/CIN I groups ( P =0.000 ),but there was no significant difference between CIN I/high-grade precancerous lesions and normal/CIN Ⅰ groups for RAR-β and MGMT.The combination of DAPK1/HR-HPV loading showed a sensitivity of 0.825 and an area under the receiver operating characteristic curve (ROC) curve (AUC) of 0.695 as diagnostic methods for detecting CIN Ⅱ/high-grade precancerous lesions.Conclusions DNA methylation such as DAPK1 and RAR-β,in combination with HR-HPV detection,may serve as biomarkers to detect CIN Ⅱ/high-grade precancerous lesions.Detection of methylated DNA from liquid-based cervical cytology specimens is technically feasible with the MS-HRM assay.

Objective To explore the pregnancy outcome and obstetric management of pregnancy and delivery after vaginal radical trachelectomy (VRT).Methods Forty-two cases of VRT from December 2003 to May 2012 in Peking Union Medical College Hospital were analyzed retrospectively.Among them ten cases got pregnant successfully.Results The average age of patient at VRT surgery was (30.6 ± 3.7) years old and average follow-up time was 29.5 months.There were 31 patients attempted conception.Ten of them got fourteen conceptions successfully.Overall conception rate was 45％ (14/31).There were four cases of first trimester abortion.Among them,two were miscarriage,two were elective abortion.There was one case of ectopic pregnancy operation and non of second trimester loss.Nine cases reached the third trimester.The total preterm delivery rate was 4/9.There were two cases delivered before 32 gestational weeks (2/9).Cesarean section was performed through a transverse incision in all of nine cases.No uterine rupture and postpartum hemorrhage occurred.All newborns had good outcomes.The average follow-up time after postpartum was 22.9 months.All cases were disease-free.Conclusions The conception rate of patients after VRT in our series is 45％.The preterm birth rate of pregnancy after VRT is higher.Routine cerclage of cervix during VRT procedure and pregnancy is not necessary.Cesarean section shortly after full term pregnancy through a transverse incision should be considered as a suitable and safe procedure.

Objective To determine the clinicopathologic characteristics of mucinous borderline ovarian tumors (MBOT) and evaluate the risk factors for recurrence. Methods A retrospective study included age, the level of Preoperative serum CA125, surgical procedures, surgical-staging and the risk factors for recurrence in 130 patients with MBOT who were treated from Jan. 1994 to Dec. 2008 in Peking Union Medical College Hospital was done. Results Preoperative serum CA125 and CA199 were elevated in 34% (33/96) and 50% (13/26) of patients respectively. Fifty-two radical surgeries included total hysterectomy and bilateral saipingo-oovarectomy (THBSO) and 78 fertility-sparing surgeries included 54salpingo-oovarectomies (SO) and 24 cystectomy were done. Fifty-five cases underwent comprehensive surgical staging. Mean size of the tumors was (16 ± 10)cm and 90. 0% (117/130) were limited to unilateral ovary. There were 59 (45.4%) cases, 62 (47.7%o) cases, 2 (1.5%) cases and 7 (5.4%) cases in stage Ⅰa, Ⅰc, Ⅱ , Ⅲ , respectively. Forty-five(34.6%)concurrent with benign mucinous tumors, 14(10.8%)ovarian intraepithelial carcinoma, 8 (6.2%) micro-invasive carcinoma and 4 (3.1%) pseudomyxoma peritonei were found. Median duration for follow-up was 56.3 months. Sixteen (12.3%) recurrences and 2 tumor related deaths were found. Median duration from surgery to recurrence was 25.6 months. Recurrent rate after THBSO(4%, 2/49)was significantly lower than that of SO(13%, 7/54) and cystectomy (17%,4/24; P ＜ 0.05). The recurrent rate of Ⅰc or Ⅲ was 18% (11/62) or 3/7, which were significantly higher than that of stage Ⅰa (3% ,2/59; P ＜0.05). Three of the 4 pseudomyxoma peritonei appeared recurrence.While,the results showed that these were no effect on recurrent rate whether concurrent intraepithelial,microinvasive carcinoma or not comprehensive staging surgery. Conclusions Majority of MBOT were diagnosed in early stage and have favorable prognosis. Patients who take conservative surgery had higher recurrence rate than those radical surgery, but it doesn't affect survival. Late stage and concurrent pseudomyxoma peritonei are risk factors for recurrence.

Objective To analyze the clinical characteristics and assess the outcome of treatment for cervical cancer during pregnancy.Methods A cohort of 13 patients with cervical cancer diagnosed during pregnancy from January 2001 to September 2011 in Peking Union Medical College Hospital (PUMCH) was retrospectively studied.Clinical information,gestational age at diagnosis,treatment options and maternal and child outcomes were collected and analyzed.Results Thirteen patients out of 2030 cases of invasive cervical cancer were diagnosed during pregnancy with an incidence of 0.64％ (13/2030).The Mean gestational age at diagnosis of 13 patients is 21+6 weeks.Two cases were diagnosed during the first trimester,8 cases at second trimester and 3 cases at third trimester respectively.Vaginal bleeding during the pregnancy was main clinical manifestation presented in 8 patients and all thirteen cases were diagnosed by biopsy with pathological types of squamous cell carcinoma in 10 cases.The International Federation of Gynecology and Obstetrics (FIGO) stage was Ⅰ in eleven cases and stage Ⅱ in two cases.Six patients of them received treatment promptly after diagnosis.The other 7 patients had delayed treatment with mean diagnosis-treatment interval time of 65 days due to fertility reasons,who ended pregnancy by cesarean section at mean gestational age of 34+6 weeks,two of them received chemotherapy with cisplatin + fiuorouracil (PF)or cisplatin respectively before the end of the pregnancy,while the one with PF chemotherapy experienced neonatal death.The rest 6 neonatal outcomes were good.As follow-up of 13 cases:11 cases in stage Ⅰ received surgical treatment,and two of which had recurrence respectively,15 months and 7 months post surgery,and one case had died.One case of Stage Ⅱ patients died and one had recurrence after 53 months after radiotherapy.The recurrence rate in 13 cases was 3/13 and the mortality rate was 2/13.Conclusions Most cases of cervical cancer diagnosed during pregnancy were in early FIGO stage.For those patients diagnosed in late pregnancy with strong fertility demand,considering delayed treatment according to FIGO stage of the disease and fetus maturity is appropriate.Chemotherapy during pregnancy may cause neonatal complications.

OBJECTIVE: To explore the genetic basis for a case of Lamb-Shaffer syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing. RESULTS: The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
Animals ; Genomics ; Heterozygote ; Humans ; Mutation ; SOXD Transcription Factors/genetics* ; Sheep ; Whole Exome Sequencing

Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.