Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer.

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.

Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis.

OBJECTIVE: Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. METHODS: We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. RESULTS: Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24-3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64-0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43-13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. CONCLUSION: According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

Non-mechanical self-alignment system for free-space optical communications based on a cascaded liquid crystal optical antenna.

Free-space optical (FSO) communication has attracted extensive attention in recent years. To maintain a reliable FSO link, two main issues need to be addressed: beam drift and vibration. In this paper, we demonstrate a non-mechanical self-alignment system based on a cascaded liquid crystal optical antenna, in which a frequency decoupled hybrid integration Kalman filter (FDHI-KF) method is proposed to achieve predictive beam drift tracking and vibration mitigation. By leveraging the integrated control on our lab-made liquid crystal phase modulation devices, and implementing the adaptive algorithm on a heterogeneous field programmable gate array (FPGA), this system is capable of realizing precise self-alignment without any moving parts. Experiments are conducted to verify its performance in practical applications. We envision it to set a benchmark for future liquid crystal non-mechanical beam-steering systems in FSO communications.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Fast, closed-loop iterative system-on-chip of deflection efficiency enhancement for a liquid crystal optical phased array.

To implement a liquid crystal optical phased array (LC-OPA) on a practical free-space laser communication terminal, there are two essential parameters: insertion loss and the closed-loop bandwidth required to meet the dynamic linking condition of the acquisition-tracking-pointing sub-system. Real-time hardware platforms and deflection efficiency optimization algorithms have been suggested since the invention of LC-OPA. In this paper, the so-called ZYNQ platform, a field-programmable-gate-array-based heterogeneous system-on-chip (SoC), is utilized to keep real-time response and accelerate data generation, such as beam steering, beamforming, beam enhancement, etc. In addition, a novel, to the best of our knowledge, optimization algorithm is proposed on the concept of dimension reduction of the number of objective variables. After deploying on this heterogeneous SoC platform, numerical simulations and experimental results both verify that, compared to the conventional PC-based system, the integrated SoC platform offers 15.8 times faster iterative speed, a rapid convergence rate, and excellent robustness, yet with less usage of power, physical size, and monetary cost. The efficiency enhancement process costs only a few seconds at any angle, laying the foundation for practical in-line applications.

An assessment of the analytical performance of non-invasive prenatal testing (NIPT) in detecting sex chromosome aneuploidies: 34,717-patient sample in a single prenatal diagnosis Centre in China.

OBJECTIVE: The present study aimed to evaluate the efficacy of a non-invasive prenatal test (NIPT) in the detection of the sex chromosome aneuploidies (SCAs) at our prenatal diagnosis centre. METHODS: Among a cohort of 34,717 pregnancies, maternal plasma samples from our prenatal diagnosis centre were subject to analysis of SCAs using NIPT detection. Pregnant women with NIPT positive results of SCAs were recommended to undergo an invasive prenatal diagnosis (i.e. karyotyping and fluorescence in situ hybridization) to validate the prediction value of NIPT. RESULTS: From 34,717 clinical pregnancies, 229 (0.66%) pregnancies were identified with SCAs. Of these, 78 (34.1%) cases were positive for 45,X and 151 (65.9%) cases comprised a sex chromosome trisomy. Of the 229 positive NIPT results, 193 (84.3%) cases had accepted an invasive diagnosis involving karyotyping analysis of the amniotic fluid, which confirmed 67 cases (34.7%) as true positive, as well as 126 cases (65.3%) as false positive. The positive predictive values were 23.07%, 50%, 36% and 27.27% respectively. The remaining 36 (15.7%) cases declined a prenatal diagnosis. The termination rates of 45,X, 47,XXY, 47,XXX and 47,XYY were 20.5%,46%,12.9% and 11.5% respectively. CONCLUSIONS: NIPT demonstrated a lower accuracy in predicting monosomy X than sex chromosome trisomies. After invasive testing, the fetal chromosome with 45,X and 47,XXY were terminated more often than those with 47,XXX, 47,XYY. Because NIPT is a screening test, false positive/negative cases exist, and pre- and post-test counselling is essential for informing patients about the benefits and limitations of the test. Confirmatory testing of abnormal results is recommended prenatally or after birth, and the importance of confirmatory testing and benefits of early diagnosis should be addressed.

circ0000069 promotes cervical cancer cell proliferation and migration by inhibiting miR-4426.

Circular RNAs (circRNAs) have been shown to be associated with the occurrence and development of cervical cancer (CC). In the present study, we aimed to investigate the tumor-promoting effect of hsa_circ_0000069 (circ0000069) on CC and the mechanisms underlying its effect. We found that circ0000069 was upregulated in CC cells and tissues, and that N6-methyladenosine (m6A) modification maintained circ0000069 stability. Gain- and loss-of-function assays revealed that circ0000069 promoted CC cell proliferation and migration. miR-4426 specifically binds circ0000069 and mediates its functions in CC development. In conclusion, circ0000069 was upregulated partially due to m6A modification, which promoted cell proliferation and migration via sponging miR-4426 in CC.

vNOTES Hysterectomy with Sentinel Lymph Node Mapping for Endometrial Cancer: Description of Technique and Perioperative Outcomes.

STUDY OBJECTIVE: To explore the technique and clinical value of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) in hysterectomy and sentinel lymph node (SLN) mapping for endometrial cancer by comparing its perioperative outcomes with those of laparoscopic staging. DESIGN: Retrospective cohort study. SETTING: Department of gynecology at a tertiary medical center. PATIENTS: All women diagnosed with endometrial cancer who underwent minimally invasive surgery at our center between August 2017 and May 2020. INTERVENTIONS: Both vNOTES and laparoscopic approaches were used for hysterectomy and SLN mapping. The success of SLN detection as well as perioperative outcomes were subsequently analyzed. MEASUREMENTS AND MAIN RESULTS: This study included 74 patients; 23 patients underwent vNOTES surgery, whereas 51 underwent standard laparoscopic surgery. The total successful SLN detection was 95.7% in the vNOTES group and 92.2% in the laparoscopy group (p >.05), whereas the bilateral success rates were 87.0% and 90.2%, respectively. No difference in SLN detection was observed between the 2 groups in terms of the side-specific mapping efficacy quotient (91.3% vs 91.2%, p = .47). The number of harvested SLNs, operative time, estimated blood loss, and intraoperative complications in the 2 groups were similar. One (4.3%) postoperative complication occurred in the vNOTES group vs 4 (7.9%) in the laparoscopy group (p = .029), and the median postoperative hospital stay was 3 days vs 4 days (p = .003). CONCLUSION: This study suggests that the vNOTES procedure is feasible, with a potentially decreased postoperative hospital stay, faster recovery, and better cosmetic results. However, prospective research is needed to validate its broader clinical application.

Short-term ambient nitrogen dioxide exposure is associated with increased risk of spontaneous abortion: A hospital-based study.

There are increasing concerns with regard to spontaneous abortion (SAB), the loss of pregnancy without external intervention before 20 weeks of gestation, among reproductive-aged women. To date, limited evidence is available concerning the association between SAB and air pollutants, especially in developing countries. Daily baseline outpatient data for SAB from January 1, 2014, to December 31, 2018 (1826 days) were obtained in Chongqing, a metropolis of southwest China. The over-dispersed Poisson generalized additive model with control of meteorological conditions and day of week was used to estimate the short-term effects of ambient air pollution on the daily number of SAB outpatients. A total of 42,334 SAB outpatient visits for SAB were recorded. No statistically significant association was observed between SAB and CO, PM2.5, PM10, O3, and SO2. The positive association only appeared for NO2: positive associations between SAB and NO2 were observed in both single-day models (lag 0, lag 1, lag 3, and lag 4) and cumulative exposure models (lag 01, lag 03, and lag 05) and the most significant effects were observed at lag 05 (3.289%; 95% CI: 1.568%, 5.011%). Moreover, the women with higher ages (30-39 and > 39) were more sensitive than those with lower ages (18-29), and the effect estimates were more evident in cool seasons. Collectively, our results suggested that short-term NO2 exposure was associated with higher risk of SAB, especially in elder women and cool seasons, which may contribute to further understand the role of air pollution on SAB and other adverse obstetric outcomes.

Study on the effect and mechanism of NFKBIA on cervical cancer progress in vitro and in vivo.

AIM: NFKBIA is frequently encountered. However, its expression and relevance of the proliferation, invasion, and migration in human cervical cancer (CC) remain unclear. The role and novel mechanism of NFKBIA in CC progression were investigated in this study. METHODS: We analyzed the expression of NFKBIA in CC and adjacent normal tissues and explored the proliferation, migration, and invasion of HeLa cells by treating with either wild-type NFKBIA plasmid or NFKBIA siRNA. Effect of NFKBIA on the epithelial-mesenchymal transition (EMT) and the ß-catenin-mediated transcription of target genes were evaluated subsequently. RESULTS: NFKBIA expression was lower in CC tissues than that of adjacent tissues. An obvious dysregulation of NFKBIA overexpression was revealed in CC cell proliferation, invasion, and migration, which differed from the effect of knockdown NFKBIA. NFKBIA overexpression facilitated the expression of both phosphorylated ß-catenin and E-cadherin protein. It inhibited the expression of vimentin, TWIST, as well as downstream targets of ß-catenin including c-MYC, TCF-4 and MMP14. Conversely, NFKBIA silencing elevated the expression of c-MYC, TCF-4, and MMP14, and promoted the EMT in HeLa cells. Both endogenous and exogenous NFKBIA interacted with ß-catenin. Moreover, ß-catenin overexpression stemmed effects of NFKBIA on the proliferation, migration, and invasion of HeLa cells. By overexpressing NFKBIA in vivo, the volume and size of tumors were notably decreased, while no obvious alteration was found in mice body weight. CONCLUSION: By inhibiting ß-catenin-mediated transcription, NFKBIA functioning as a tumor suppressor might be introduced as a novel anti-metastatic agent for the treatment of targeted CC.

Effect of laparoscopic versus abdominal radical hysterectomy on major surgical complications in women with stage IA-IIB cervical cancer in China, 2004-2015.

OBJECTIVES: To report the trends in surgical approaches and compare the major surgical complication rates of laparoscopic and abdominal radical hysterectomy for cervical cancer. METHODS: From the major surgical complications of cervical cancer in China (MSCCCC) database, we obtained the demographic, clinical, treatment hospital and complication data of patients with cervical cancer who underwent radical hysterectomy from 2004 to 2015 at 37 hospitals. The patients were assigned to the laparoscopic and abdominal surgery groups. The differences in the complication rates were analyzed using univariate and multivariable logistic regression models. RESULTS: We identified a total of 18447 patients; 5491 (29.8%) underwent laparoscopic surgery and 12956 (70.2%) underwent abdominal surgery. The proportion of laparoscopic surgery rose from 0.35% in 2004 to 49.31% in 2015. In the multivariate analysis, the laparoscopic group had increased odds of intraoperative and postoperative complications (OR = 3.88, 95% CI = 2.47-6.11; OR = 1.42, 95% CI = 1.11-1.82). A more detailed analysis showed that laparoscopic surgery was associated with increased rates of intraoperative ureteral injury (OR = 3.83, 95% CI = 2.11-6.95), bowel injury (OR = 14.83, 95% CI = 1.32-167.25), vascular injury (OR = 3.37, 95% CI = 1.18-9.62), postoperative vesicovaginal fistula (OR = 4.16, 95% CI = 2.08-8.32), ureterovaginal fistula (OR = 4.16, 95% CI = 2.08-8.32), rectovaginal fistula (OR = 8.04, 95% CI = 1.63-39.53), and chylous leakage (OR = 10.65, 95% CI = 1.18-95.97), while abdominal surgery was more likely to cause bowel obstruction (OR = 0.55, 95% CI = 0.35-0.87). The two groups had similar rates of bladder injury, obturator nerve injury, pelvic hematoma, rectovaginal fistula and venous thromboembolism (P > 0.05). CONCLUSION: Laparoscopic surgery was associated with more major surgical complications, especially intraoperative ureteral injury and postoperative fistula, than abdominal surgery among women with cervical cancer.

Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning.

BACKGROUND: To better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC. METHODS: We performed whole-genome sequencing or whole-exome sequencing of 102 tumour-normal pairs and human papillomavirus probe capture sequencing of 45 CCs, 44 CIN samples and 25 normal cervical samples, and constructed strict integrated workflow of genomic analysis. RESULTS: Mutational analysis identified eight significantly mutated genes in CC including four genes (FAT1, MLL3, MLL2 and FADD), which have not previously been reported in CC. Targetable alterations were identified in 55.9% of patients. In addition, HPV integration breakpoints occurred in 97.8% of the CC samples, 70.5% of the CIN samples and 42.8% of the normal cervical samples with HPV infection. Integrations of high-risk HPV strains in CCs, including HPV16, 18, 33 and 58, also occurred in the CIN samples. Moreover, gene mutations were detected in 52% of the CIN specimens, and 54.8% of these mutations occurred in genes that also mutated in CCs. CONCLUSION: Our results lay the foundation for a deep understanding of the molecular mechanisms and finding new diagnostic and therapeutic targets of CC.

Association between air pollution and menstrual disorder outpatient visits: A time-series analysis.

Menstrual disorders are common diseases among reproductive-aged women with increasing concerns. Until now, there have been limited studies about the association between menstrual disorders and air pollution. This study aimed to investigate the association between short-term (concurrent day and within 1 week prior) ambient air pollution exposure and menstrual disorder outpatient visits in Xi'an, a metropolis in northwestern China. Daily baseline outpatient data of menstrual disorders from January 1, 2010 to February 18, 2016 (2239 days) were obtained. An over-dispersed Poisson generalized additive model was applied to discover the relationship between short-term air pollution exposure and the number of menstrual disorder outpatient visits by adjusting the day of the week and weather conditions. A total of 51,893 outpatient visits for menstrual disorders were recorded. A 10 µg/m3 increase of PM10 and NO2 concentrations corresponded to 0.236% (95% Cl: 0.075%, 0.397%) and 2.173% (95% Cl: 0.990%, 3.357%) elevations in outpatient-visits for menstrual disorders at lag 7 and lag 01 (concurrent day and previous 1 day), respectively. The association was more significant in young females (18-29 years) and there was no obvious association observed between SO2 and menstrual disorder outpatient visits. This is the first evidence that short-term exposure to ambient air pollution can be associated with an increased risk of menstrual disorder attacks. The results of our study may help to establish more comprehensive understanding of the health effects of ambient air pollution on menstrual disorders and other reproductive diseases.

Targeted next-generation sequencing identification of mutations in patients with disorders of sex development.

BACKGROUND: The identification of causative mutations is important for treatment decisions and genetic counseling of patients with disorders of sex development (DSD). Here, we designed a new assay based on targeted next-generation sequencing (NGS) to diagnose these genetically heterogeneous disorders. METHODS: All coding regions and flanking sequences of 219 genes implicated in DSD were designed to be included on a panel. A total of 45 samples were used for sex chromosome dosage validation by targeted sequencing using the NGS platform. Among these, 21 samples were processed to find the causative mutation. RESULTS: The sex chromosome dosages of all 45 samples in this assay were concordant with their corresponding karyotyping results. Among the 21 DSD patients, a total of 11 mutations in SRY, NR0B1, AR, CYP17A1, GK, CHD7, and SRD5A2 were identified, including five single nucleotide variants, three InDels, one in-frame duplication, one SRY-positive 46,XX, and one gross duplication with an estimated size of more than 427,038 bp containing NR0B1 and GK. We also identified six novel mutations: c.230_231insA in SRY, c.7389delA in CHD7, c.273C>G in NR0B1, and c.2158G>A, c.1825A>G, and c.2057_2065dupTGTGTGCTG in AR. CONCLUSIONS: Our assay was able to make a genetic diagnosis for eight DSD patients (38.1%), and identified variants of uncertain clinical significance in the other three cases (14.3%). Targeted NGS is therefore a comprehensive and efficient method to diagnose DSD. This work also expands the pathogenic mutation spectrum of DSD.

Laparoscopy versus laparotomy for the management of early stage cervical cancer.

BACKGROUND: The possible advantages of laparoscopic radical hysterectomy (LRH) versus open radical hysterectomy (RH) have not been well reviewed systematically. The aim of this study was to systematically review the comparative effectiveness between LRH and RH in the treatment of cervical cancer based on the evaluation of the Perioperative outcomes, oncological clearance, complications and long-term outcomes. METHODS: The systematic review was conducted by searching PubMed, MEDLINE, EMBASE, the Cochrane Library and BIOSIS databases. All original studies that compared LRH with RH were included for critical appraisal. Data were pooled and analyzed. RESULTS: A total of twelve original studies that compared LRH (n = 754) with RH (n = 785) in patients with cervical cancer fulfilled quality criteria were selected for review and meta-analysis. LRH compared with RH was associated with a significant reduction of intraoperative blood loss (weighted mean difference = -268.4 mL (95 % CI -361.6, -175.1; p < 0.01), a reduced risk of postoperative complications (OR = 0.46; 95 % CI 0.34-0.63) and shorter hospital stay (weighted mean difference = -3.22 days; 95 % CI-4.21, -2.23 days; p < 0.01). These benefits were at the cost of longer operative time (weighted mean difference = 26.9 min (95 % CI 8.08-45.82). The rate of intraoperative complications was similar in the two groups. Lymph nodes yield and positive resection margins were similar between the two groups. There were no significant differences in 5-year overall survival (HR 0.91, 95 % CI 0.48-1.71; p = 0.76) and 5-year disease-free survival (hazard ratio [HR] 0.97, 95 % CI 0.56-1.68; p = 0.91). CONCLUSIONS: LRH shows better short term outcomes compared with RH in patients with cervical cancer. The oncologic outcome and 5-year survival were similar between the two groups.

Surface invasive cleavage assay on a maskless light-directed diamond DNA microarray for genome-wide human SNP mapping.

The surface invasive cleavage assay, because of its innate accuracy and ability for self-signal amplification, provides a potential route for the mapping of hundreds of thousands of human SNP sites. However, its performance on a high density DNA array has not yet been established, due to the unusual "hairpin" probe design on the microarray and the lack of chemical stability of commercially available substrates. Here we present an applicable method to implement a nanocrystalline diamond thin film as an alternative substrate for fabricating an addressable DNA array using maskless light-directed photochemistry, producing the most chemically stable and biocompatible system for genetic analysis and enzymatic reactions. The surface invasive cleavage reaction, followed by degenerated primer ligation and post-rolling circle amplification is consecutively performed on the addressable diamond DNA array, accurately mapping SNP sites from PCR-amplified human genomic target DNA. Furthermore, a specially-designed DNA array containing dual probes in the same pixel is fabricated by following a reverse light-directed DNA synthesis protocol. This essentially enables us to decipher thousands of SNP alleles in a single-pot reaction by the simple addition of enzyme, target and reaction buffers.

[Randomized, blind, parallel-controlled and multiple-centre clinical trial on the effectiveness and safety of leuprolide acetate in the treatment of endometriosis].

OBJECTIVE: To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis. METHODS: From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient's subjective symptoms during non-menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed. RESULTS: After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P = 0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5% (48/101) in the test group, 44.0% (44/100) in the control group, P = 0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33±38) pmol/L in the test group, (38±40) pmol/L in the control group, P = 0.414; the serum level of FSH, was (5.1±2.8) U/L in the test group, (5.3±2.3) U/L in the control group, P = 0.666; the serum level of LH, was (0.6±0.8) U/L in the test group, (0.6±0.9) U/L in the control group, P = 0.907], had no statistically significant difference between the two groups (all P > 0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9% (34/46), 15.2% (7/46) respectively in the test group, 72.3% (34/47), 2.1% (1/47) respectively in the control group, had statistically significant difference between the two groups (P = 0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6% (38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P = 0.082). CONCLUSION: Leuprolide acetate is effective and safe in the treatment of endometriosis.

A robust approach for blind detection of balanced chromosomal rearrangements with whole-genome low-coverage sequencing.

Balanced chromosomal rearrangement (or balanced chromosome abnormality, BCA) is a common chromosomal structural variation. Next-generation sequencing has been reported to detect BCA-associated breakpoints with the aid of karyotyping. However, the complications associated with this approach and the requirement for cytogenetics information has limited its application. Here, we provide a whole-genome low-coverage sequencing approach to detect BCA events independent of knowing the affected regions and with low false positives. First, six samples containing BCAs were used to establish a detection protocol and assess the efficacy of different library construction approaches. By clustering anomalous read pairs and filtering out the false-positive results with a control cohort and the concomitant mapping information, we could directly detect BCA events for each sample. Through optimizing the read depth, BCAs in all samples could be blindly detected with only 120 million read pairs per sample for data from a small-insert library and 30 million per sample for data from nonsize-selected mate-pair library. This approach was further validated using another 13 samples that contained BCAs. Our approach advances the application of high-throughput whole-genome low-coverage analysis for robust BCA detection-especially for clinical samples-without the need for karyotyping.

Distinct karyotypes in two offspring of a man with jumping translocation karyotype 45,XY,der(16)t(16;22)(q24;q11.2), -22 [59]/45,XY,der(1)t(1;22)(p36;q11.2), -22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), -22 [10].

We examined a man and his daughter, who both had different jumping translocation karyotypes. The man's wife was pregnant and had been referred for prenatal diagnosis of the fetus. The karyotype of the husband's peripheral blood lymphocytes was 45,XY,der(16)t(16;22)(q24;q11.2), -22 [59]/45,XY,der(1)t(1;22)(p36;q11.2), -22 [11]/45,XY,der(22)t(22;22)(p13;q11.2), -22 [10]. The karyotype of the daughter's peripheral blood lymphocytes was 45,XX,der(16)t(16;22)(q24;q11.2), -22 [45]/45,XX,der(9)t(9;22)(q34;q11.2), -22 [30]/45,XX,der(5)t(5;22)(q35;q11.2), -22 [25]. The wife and the fetus both had a normal karyotype. To the best of our knowledge, the present familial transmitted jumping translocation has not been previously described and the jumping translocation in the husband and daughter did not cause any phenotypic abnormalities.