Gonadotropin-releasing hormone agonist versus expectant management for treating multiple leiomyomas after myomectomy: the study protocol for a multicentre, prospective, randomised controlled clinical trial.

INTRODUCTION: Leiomyoma recurrence is a major concern for long-term myomectomy management, especially for multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is one of the most effective medications to reduce the volume of fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no randomised clinical trial determining the efficacy of GnRHa treatment for preventing multiple leiomyomas recurrence after myomectomy. METHODS AND ANALYSIS: We are conducting a phase IV randomised controlled trial in women aged 18-45 undergoing myomectomy for multiple leiomyomas. After surgery, women whose pathological result confirms multiple leiomyomas are randomised in a 1:1 ratio into an observation or GnRHa group. The primary outcome is the recurrence of either clinical symptoms or fibroids on imaging. Patients will be assessed for adverse events during the follow-up. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee of the Tongji Hospital Affiliated with the Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180311) according to the submitted study protocol (V.1.0, 10 November 2017) and informed consent (V.1.0, 10 November 2017). The results will be presented at domestic and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17012992.

Early response to neoadjuvant chemotherapy helps decrease recurrence rate of cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Neoadjuvant chemotherapy has been used for treatment of cervical cancer for a long time; however, the role of early non-response on prognosis is still confusing. This study was designed to assess its impact on disease-free survival (DFS). METHODS: Databases "PubMed", "Embase" and the "Cochrane Library" were searched out through May 2020, and both random effects model and fixed effect model were employed to calculate the main pooled results. I2 and Cochrane Q test were used to test the heterogeneity among the studies. Funnel plot with Begg's and Egger's tests was used to assess the publication bias that may exist in the study. Sensitivity analysis was performed to detect the origin of the heterogeneity. RESULTS: A total of 1,349 articles were found at first; then, after several rounds of exclusion, we identified 8 articles with 9 studies which were accordant with the standards of the inclusion. A combined analysis was performed among the 1,462 responders and 490 non-responders. For 1-year DFS, sub-analysis showed hazard ratio (HR) was 0.25 (95% CI: 0.14-0.43) using RECIST criteria; and HR was 0.52 (95% CI: 0.36-0.75) using WHO criteria; Egger's test showed that P=0.35 for RECIST criteria and P=0.57 for WHO criteria; Begg's test showed P=0.34 for RECIST criteria and P=0.60 for WHO criteria. For 3-year DFS, HR was 0.26 (95% CI: 0.16-0.43) using RECIST criteria and was 0.47 (95% CI: 0.30-0.73) using WHO criteria. For 5-year DFS, HR was 0.26 (95% CI: 0.16-0.42) using RECIST criteria and was 0.49 (95% CI: 0.33-0.71) using WHO criteria. DISCUSSION: Early non-response to neoadjuvant chemotherapy was significantly associated with higher recurrence of cervical cancer. Prospective randomized studies are warranted to validate this finding.

MiR-204-5p/TFAP2A feedback loop positively regulates the proliferation, migration, invasion and EMT process in cervical cancer.

MicroRNAs (MiRNAs) have been clarified as crucial regulators of the pathological processes in various carcinomas in the past years. Interestingly, existing evidence has manifested that microRNA-204-5p (miR-204-5p) is engaged in the initiation and progression of multiple carcinomas. However, the potential of miR-204-5p in cervical cancer remains to be disentombed. This study focused on unraveling the detailed role of miR-204-5p in cervical cancer. MiR-204-5p exhibited a low level in cervical cancer cells. The functional assays demonstrated that miR-204-5p upregulation exerted suppressive impact on the functions of cervical cancer cells, including proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) process. Moreover, transcription factor AP-2 alpha (TFAP2A) was screened to be the most affected target gene by miR-204-5p, and TFAP2A was discovered to transcriptionally repress miR-204-5p in cervical cancer. The mutual regulation between TFAP2A and miR-204-5p was testified through molecular mechanism assays. Final rescued-function assays demonstrated that overexpression of TFAP2A could recover the suppressed cellular process caused by miR-204-5p upregulation. In conclusion, miR-204-5p/TFAP2A feedback loop promoted the proliferative and motorial capacities of cervical cancer cells. This finding suggested a novel modulatory loop of miR-204-5p/TFAP2A in cervical cancer, offering promising biomarkers for cervical cancer therapy.

Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis: study protocol for a multicenter, prospective, randomized controlled trial.

BACKGROUND: The preservation of fertility and integrity of the reproductive organs has increasingly been of concern to most women with adenomyosis. Adenomyomectomy is conservative surgery that is now widely applied; however, relapse is a serious problem after the operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the rate of disease recurrence. However, there is still a lack of evidence from randomized clinical trials examining the efficacy of GnRHa in decreasing the postoperative recurrence rate. METHOD/DESIGN: Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse assessed using a visual analogue scale (VRS) and numeric rating scale (NRS), pictorial blood loss assessment chart (PBAC) score, and the size of the uterus and the lesion as measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, adverse events, assessment by the Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels, and anti-Muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, and 36 months after conservative surgery. DISCUSSION: The result of this large, multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014340. Registered on 6 January 2018.

Viral and bacterial coinfection among hospitalized children with respiratory tract infections.

BACKGROUND: The epidemiology of Mycoplasma pneumoniae (MP) and local dominant etiologies of pathogens that cause respiratory tract infections (RTIs) among central China children (≤14 years old) hospitalized are poorly understood. METHODS: A total of 10,429 specimens were analyzed, and IgM antibodies against 9 respiratory pathogens including MP were detected using indirect immunofluorescence assay from serum. RESULTS: It showed that 59.3% of the enrolled children were positive for at least 1 pathogen; highest detection rates included those between 3 and <6 years of age (70.4%), female (63.2%), and who were hospitalized in 2014 (80.9%). The most predominant pathogen was MP (45.6%), followed by Parainfluenza viruses (PIVs) (22.6%) and influenza B viruses (IFVB) (14.7%). Coinfection was observed in 2,907 specimens (27.9%); the coinfection combination containing MP and PIVs had the highest detection rate of 15%, followed by MP and IFVB as well as IFVB and PIVs. CONCLUSIONS: MP was the most commonly detected bacteria among hospitalized children, which should be included in the differential diagnosis for hospitalized children with RTI. These findings will contribute to the effective prevention and therapeutic approaches of pathogens among local children suffering from RTI.

Numb inhibits cell proliferation, invasion, and epithelial-mesenchymal transition through PAK1/ß-catenin signaling pathway in ovarian cancer.

OBJECTIVE: The present study aimed to investigate the expression of Numb in ovarian cancer tissues and to assess the effect of Numb on cell proliferation, invasion, and EMT in ovarian cancer. METHODS: Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Numb, PAK1, ß-catenin, and epithelial-mesenchymal transition (EMT)-related proteins. MTT was employed to check the effect of Numb on proliferation of ovarian cancer cells. Transwell assay was performed to examine the functions of Numb and PAK1 on migration and invasion of ovarian cancer cells. RESULTS: The Numb expression was significantly downregulated while PAK1 and ß-catenin were significantly upregulated in both ovarian cancer tissues and cell lines. Silencing of Numb promoted cell proliferation, migration, invasion, and EMT in ovarian cancer cell lines while overexpressed Numb reversed the above effects. Moreover, the EMT process induced by the inhibition of Numb was regulated through Numb-mediated PAK1/ß-catenin signaling pathway. CONCLUSION: Numb was downregulated and associated with cell proliferation, invasion, and EMT in ovarian cancer through regulating PAK1/ß-catenin signaling, providing a novel potential biomarker and potential therapeutic target for ovarian cancer.

Long non-coding RNA TTN-AS1 promotes cell growth and metastasis in cervical cancer via miR-573/E2F3.

Long non-coding RNAs (lncRNAs) are a crucial member of non-coding RNA family, and increasing evidence demonstrates that lncRNAs participate in the initiation and progression of cancers. Our study aimed to explore the role of lncRNA TTN-AS1 in cervical cancer (CC) development. In the present study, our results showed that TTN-AS1 was substantially increased in CC tissues and cell lines, high expression of TTN-AS1 was correlated with advanced FIGO stage, poor differentiation, lymph node metastasis, and poor overall survival of CC patients. Function assays showed that TTN-AS1 inhibition decreased the proliferation and invasion of CC cells both in vitro and in vivo. Mechanistically, we revealed that TTN-AS1 could positively modulate E2F3 expression via sponging miR-573 in CC cells. Together, our study revealed that lncRNA TTN-AS1 was involved in the progression of CC cells by regulation of miR-573-E2F3 axis, which offered a new insight into the treatment strategies of CC.

Amentoflavone suppresses tumor growth in ovarian cancer by modulating Skp2.

AIM: Ovarian cancer is one of most common malignancies in women and is associated with high reoccurrence rate and poor prognosis. This study is designed to investigate the anti-tumor effects of amentoflavone (AF), one of the major active ingredients of S. tamariscina, against ovarian cancer. MATERIALS AND METHODS: Human ovarian cancer cell lines SKOV3 and OVCAR-3 were used in this study. The effect of AF on cell viability was examined by CCK-8 assay. Cell apoptosis and cell cycle distribution was determined by flow cytometry. ROS generation was detected using fluorescent staining. Expression of signaling molecules was determined by western blots. Xenograft model was established to evaluate the therapeutic efficacy of AF in vivo. KEY FINDINGS: Our results showed that AF could significantly suppress cell proliferation, induce apoptosis and block cell cycle progression. Mechanistically, downregulation of S-phase kinase protein 2 (Skp2) by AF contributed to its anti-tumor effect against ovarian cancer. Furthermore, our results showed that AF repressed the expression of Skp2 through ROS/AMPK/mTOR signaling. The anti-tumor effect of AF against ovarian cancer was also confirmed in a xenograft animal model. SIGNIFICANCE: Overall, our present findings highlighted the potential of AF in the treatment of ovarian cancer. Moreover, our study also provided a new elucidation regarding the anti-tumor mechanisms of AF.

Liquiritin (LT) exhibits suppressive effects against the growth of human cervical cancer cells through activating Caspase-3 in vitro and xenograft mice in vivo.

Cervical cancer is one of the most common female malignancies worldwide. Liquiritin (LT), a major constituent of Glycyrrhiza Radix, possesses a variety of pharmacological activities, including anti-cancer, anti-oxidative, anti-inflammatory and neuro-protective effects. However, its role in human cervical cancer remains to be elusive. In our study, we found that LT suppressed cervical cancer cell migration, invasion and cloning ability with little cytotoxicity to human normal cells. In addition, apoptosis was induced by LT in cervical cancer cells through activation of Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage. LT-triggered apoptosis was dependent on extrinsic and intrinsic pathways, which were relied on Fas-associated protein with death domain (FADD)- and Bcl-2/Bax-regulated pathways, leading to Caspase-8 and Caspase-9 cleavage, respectively. LT was found to increase FADD expression, while reduce Bcl-2 expression, contributing to Caspase-3 cleavage. And tumor suppressors, p21 and p53, were enhanced after LT treatment, inhibiting the growth of cervical cancer cells in vitro. Significantly, in vivo study suggested that tumor growth was impeded by LT in a dose-dependent manner through enhancing apoptosis. Together, the data here revealed that LT was an effective and promising candidate for preventing human cervical cancer progression via apoptosis enhancement.