Background:Pelvic lymph node metastasis (PLNM) is the key to determining the treatment and prognosis of early-stage cervical cancer (CC, I–IIst). The aim of this study was to identify biomarkers for PLNM of CC, I–IIst.Methods:Two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to identify differentially expressed proteins in primary CC, I–IIst tissue with (n=8) and without (n=10) PLNM. The expression levels of three differential proteins (FABP5, HspB1, and MnSOD) were validated using western blotting and immunohistochemistry. An independent cohort of 105 CC, I–IIst patients was analysed to assess the correlation of FABP5, HspB1, and MnSOD with clinicopathologic factors and clinical outcomes.Results:Forty-one differential proteins were identified. Upregulation of FABP5, HspB1, and MnSOD in CC, I–IIst with PLNM was confirmed and was significantly correlated with PLNM. FABP5, HspB1, and MnSOD were significant predictors of PLNM in univariate analysis. FABP5, HspB1, and lymphovascular space invasion (LVSI) were independent predictors of PLNM in multivariate analysis. Survival curves indicated that CC, I–IIst patients with FABP5, HspB1, and MnSOD upregulation had poor prognosis.Conclusions:FABP5, HspB1, and MnSOD may be potential biomarkers for PLNM of CC, I–IIst and may have important roles in the pathogenesis of PLNM.

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STUDY QUESTION What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS Human oocytes were collected from donors aged 28–41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-μM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/β-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Purpose: The incidence and risk factors for diabetic retinopathy (DR) in southern China remains unclear. This project aims to explore the onset and progression of DR and their determinants through a prospective cohort in South China. Methods: The Guangzhou Diabetic Eye Study (GDES) recruited patients with type 2 diabetic patients registered in the community health centres in Guangzhou, China. Patients with history of ocular treatment, severe refractive opacity, or other systemic diseases were excluded. Comprehensive examinations were performed including visual acuity, refraction, ocular biometry, fundus imaging, blood and urine tests. The biological samples were collected for further study. Results: A total of 2305 eligible patients were included in the final analysis. In total, 14.58% of the participants had any DR and 4.25% had vision-threatening DR (VTDR), among which 76 (3.30%), 197 (8.55%), 45 (1.95%) and 17 (0.74%) were classified as mild NPDR, moderate NPDR, severe NPDR and PDR, respectively. There were 93 (4.03%) patients of diabetic macular edema (DME). The presence of any DR was independently associated with a longer duration of DM, higher degree of HbA1C, insulin treatment, higher average arterial pressure, higher concentration of serum creatinine, presence of urinary microalbumin, older age, and lower BMI (all P <0.001). For VTDR, 7 factors were significant: older age, a longer duration of DM, higher concentration of HbA1c, use of insulin, lower BMI, higher concentration of serum creatinine, and high albuminuria (all P<0.05). These factors were also independently associated with DME (all P <0.001). Conclusions: The GDES is the first large-scale prospective cohort study of the diabetic population in southern urban China, which will help to identify newer imaging and genetic biomarkers for DR in this population.