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To evaluate whether low coverage whole genome sequencing is suitable for the detection of malignant pelvic mass and compare its diagnostic value with traditional tumor markers. We enrolled 63 patients with a pelvic mass suspicious for ovarian malignancy. Each patient underwent low coverage whole genome sequencing (LCWGS) and traditional tumor markers test. The pelvic masses were finally confirmed via pathological examination. The copy number variants (CNVs) of whole genome were detected and the Stouffers Z-scores for each CNV was extracted. The risk of malignancy (RM) of each suspicious sample was calculated based on the CNV counts and Z-scores, which was subsequently compared with ovarian cancer markers CA125 and HE4, and the risk of ovarian malignancy algorithm (ROMA). Receiver Operating Characteristic Curve (ROC) were used to access the diagnostic value of variables. As confirmed by pathological diagnosis, 44 (70%) patients with malignancy and 19 patients with benign mass were identified. Our results showed that CA125 and HE4, the CNV, the mean of Z-scores (Zmean), the max of Z-scores (Zmax), the RM and the ROMA were significantly different between patients with malignant and benign masses. The area under curve (AUC) of CA125, HE4, CNV, Zmax, and Zmean was 0.775, 0.866, 0.786, 0.685 and 0.725 respectively. ROMA and RM showed similar AUC (0.876 and 0.837), but differed in sensitivity and specificity. In the validation cohort, the AUC of RM was higher than traditional serum markers. In conclusion, we develop a LCWGS based method for the identification of pelvic mass of suspicious ovarian cancer. LCWGS shows accurate result and could be complementary with the existing diagnostic methods. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-03046-3.

AIM To determine whether single endometrial polyp (EP) or multiple EP (polyp number ≥ 6) are associated with chronic endometritis (CE). METHODS From June 2017 to December 2018, this study enrolled a total of 277 patients, including 92 patients with multiple EP, 82 patients with a single EP and 103 patients without polyps who underwent hysteroscopic examination and polypectomy. Polyps and endometrium samples were obtained and subjected to immunohistochemistry for CD138 to identify plasma cells and CE was diagnosed as CD138-positive plasma cells greater than or equal to 5/high power field. The prevalence of CE was compared and analyzed using the logistic regression model. RESULTS All baseline parameters were comparable among the three groups except that the prevalence of abnormal uterine bleeding (AUB) was much higher in both polyp groups than the non-polyp control. The prevalence of CE was significantly higher in the multiple EP group than in the single EP group (58.7% vs 28.0%, P

Objective To investigate the therapeutic effect of antibiotic treatment on pregnancy outcomes in the following frozen-thawed embryo transfer cycles of infertile women. Design Retrospective study. Setting University assisted reproduction unit. Patient(s) A total of 640 women were included. Among them, the number of CD138+ cells per high-power field (CD138+/HPF) in the endometrium at the first evaluation was 0 in 88 women; 315 women had 1–4 CD138+/HPF and the remaining 237 had ≥5 CD138+/HPF. Finally, 26 of 237 women had persistent chronic endometritis (PCE) diagnosed. Intervention(s) Hysteroscopy and endometrial biopsy were performed in the proliferative phase. After antibiotic treatment, endometrial biopsy samples were collected again. Main Outcome Measure(s) Live birth rate. Result(s) No significant difference in pregnancy outcomes was found between women with CD138+/HPF = 0 and those with CD138+/HPF 1–4. The cure rate was 89.0% in women with CD138+/HPF ≥5 after treatment. The implantation rate (51.6% vs. 32.3%, relative risk [RR] 2.23, 95% confidence interval [CI] 1.07–4.66), clinical pregnancy rate (65.7% vs. 42.3%, RR 2.62, 95% CI 1.17–5.86), live birth rate (52.1% vs. 30.7%, RR 2.45, 95% CI 1.04–5.76), and cumulative live birth rate (64.2% vs. 38.5%, RR 2.88, 95% CI 1.27–6.51) were all significantly higher in women with CD138+/HPF ≤4 than in women with PCE. Conclusion(s) CD138+/HPF ≤4 in the endometrium had no negative impact on pregnancy outcomes. Antibiotic treatment was an effective way to improve the reproductive outcomes of women with CD138+/HPF ≥5. PCE was associated with poorer pregnancy outcomes.

Genome editing tools targeting high-risk human papillomavirus (HPV) oncogene could be a promising therapeutic strategy for the treatment of HPV-related cervical cancer. We aimed to improve the editing efficiency and detect off-target effects concurrently for the clinical translation strategy by using CRISPR-Cas9 system co-transfected with 34nt non-homologous double-stranded oligodeoxynucleotide (dsODN). We firstly tested this strategy on targeting the Green Fluorescent Protein (GFP) gene, of which the expression is easily observed. Our results showed that the GFP+ cells were significantly decreased when using GFP-sgRNAs with dsODN, compared to using GFP-sgRNAs without donors. By PCR and Sanger sequencing, we verified the dsODN integration into the break sites of the GFP gene. And by amplicon sequencing, we observed that the indels% of the targeted site on the GFP gene was increased by using GFP-sgRNAs with dsODN. Next, we went on to target the HPV18 E7 oncogene by using single E7-sgRNA and multiplexed E7-sgRNAs respectively. Whenever using single sgRNA or multiplexed sgRNAs, the mRNA expression of HPV18 E7 oncogene was significantly decreased when adding E7-sgRNAs with dsODN, compared to E7-sgRNAs without donor. And the indels% of the targeted sites on the HPV18 E7 gene was markedly increased by adding dsODN with E7-sgRNAs. Finally, we performed GUIDE-Seq to verify that the integrated dsODN could serve as the marker to detect off-target effects in using single or multiplexed two sgRNAs. And we detected fewer on-target reads and off-target sites in multiplexes compared to the single sgRNAs when targeting the GFP and the HPV18 E7 genes. Together, CRISPR-Cas9 system co-transfected with 34nt dsODN concurrently improved the editing efficiency and monitored off-target effects, which might provide new insights in the treatment of HPV infections and related cervical cancer.

Human papillomavirus (HPV) integrating into human genome is the main cause of cervical carcinogenesis. HPV integration selection preference shows strong dependence on local genomic environment. Due to this theory, it is possible to predict HPV integration sites. However, a published bioinformatic tool is not available to date. Thus, we developed an attention-based deep learning model DeepHPV to predict HPV integration sites by learning environment features automatically. In total, 3608 known HPV integration sites were applied to train the model, and 584 reviewed HPV integration sites were used as the testing dataset. DeepHPV showed an area under the receiver-operating characteristic (AUROC) of 0.6336 and an area under the precision recall (AUPR) of 0.5670. Adding RepeatMasker and TCGA Pan Cancer peaks improved the model performance to 0.8464 and 0.8501 in AUROC and 0.7985 and 0.8106 in AUPR, respectively. Next, we tested these trained models on independent database VISDB and found the model adding TCGA Pan Cancer performed better (AUROC: 0.7175, AUPR: 0.6284) than the model adding RepeatMasker peaks (AUROC: 0.6102, AUPR: 0.5577). Moreover, we introduced attention mechanism in DeepHPV and enriched the transcription factor binding sites including BHLHA15, CHR, COUP-TFII, DMRTA2, E2A, HIC1, INR, NPAS, Nr5a2, RARa, SCL, Snail1, Sox10, Sox3, Sox4, Sox6, STAT6, Tbet, Tbx5, TEAD, Tgif2, ZNF189, ZNF416 near attention intensive sites. Together, DeepHPV is a robust and explainable deep learning model, providing new insights into HPV integration preference and mechanism. Availability: DeepHPV is available as an open-source software and can be downloaded from https://github.com/JiuxingLiang/DeepHPV.git, Contact: huzheng1998@163.com, liangjiuxing@m.scnu.edu.cn, lizheyzy@163.com

The perceptual load theory of attentional selection argues that the degree to which distractors interfere with target processing is determined by the "perceptual load" (or discrimination difficulty) of target processing: when perceptual load is low, distractors interfere to a greater extent than when it is high. A well-known exception is load-independent interference effects from face distractors during processing of name targets. This finding was reconciled with load theory by proposing distinct processing resources for faces versus names. In the present study, we revisit this effect to test (a) whether increasing the processing overlap (perceptual, lexical, conceptual) between potential targets and distractors would reinstate the classic load effect, and (b) whether this data pattern could be better explained by load theory or by a rival account that argues that distractor dilution rather than target load determines the degree of distractor interference. Over four experiments, we first replicate the original finding and then show that load effects grow with increasing processing overlap between potential targets and distractors. However, by adding dilution conditions, we also show that these processing overlap dependent modulations of distractor interference can be explained by the distractor dilution perspective but not by perceptual load theory. Thus, our findings support a processing overlap dilution account of attentional selection.

The fact that interference from peripheral distracting information can be reduced in high perceptual load tasks has been widely demonstrated in previous research. The modulation from the perceptual load is known as perceptual load effect (PLE). Previous functional magnetic resonance imaging (fMRI) studies on perceptual load have reported the brain areas implicated in attentional control. To date, the contribution of attentional control to PLE and the relationship between the organization of functional connectivity and PLE are still poorly understood. In the present study, we used resting-state fMRI to explore the association between the voxel-wise degree centrality (DC) and PLE in an individual differences design and further investigated the potential resting-state functional connectivity (RSFC) contributing to individual’s PLE. DC-PLE correlation analysis revealed that PLE was positively associated with the right middle temporal visual area (MT)—one of dorsal attention network (DAN) nodes. Furthermore, the right MT functionally connected to the conventional DAN and the RSFCs between right MT and DAN nodes were also positively associated with individual difference in PLE. The results suggest an important role of attentional control in perceptual load tasks and provide novel insights into the understanding of the neural correlates underlying PLE.

Objective. To evaluate the characteristics and antiangiogenic effects of endostatin-loaded PAMAM on endometriosis in a noninvasive animal model.Materials and Methods. A noninvasive animal model was established by injecting adenovirus-GFP transfected endometrial stromal and glandular epithelial cells subcutaneously into nude mice. Endostatin-loaded PAMAM was prepared and identified by transmission electron microscopy. Forin vitrostudies, the DNA protection and cytotoxicity of PAMAM were investigated and compared with Lipofectamine 2000. Forin vivostudy, endostatin-loaded PAMAM was injected into the noninvasive model and evaluated by continuously observing the fluorescent lesion, lesion weight, microvessel density and VEGF immunostaining.Results. Compared with Lipofectamine 2000, PAMAM and HC PAMAM-ES group, MC PAMAM-ES group and LC PAMAM-ES group demonstrated a better stromal cells protective such that MC PAMAM-ES group of CCK8 was 0.617 ± 0.122 at 24 hr and 0.668 ± 0.143 at 48 hr and LC PAMAM-ES group of CCK8 was 0.499 ± 0.103 at 24 hr and 0.610 ± 0.080 at 48 hr in stromal cells (P<0.05) but similar cytotoxicity in glandular epithelial cellsin vitro. After 16 hrs of digestion, DNA decreased slightly under the protection of PAMAM. Endostatin-loaded PAMAM of HD PAMAM-ES group and LD PAMAM-ES group inhibited the growth of the endometriotic lesionin vivoat days 15, 20, 25 and 30 detected by noninvasive observation after injecting one dose endostatin of various medicines into the endometrial lesion in each mouse on day 10 (P<0.05) and confirmed by lesion weight at day 30 with HD PAMAM-ES group being 0.0104 ± 0.0077 g and LD PAMAM-ES group being 0.0140 ± 0.0097 g (P<0.05). Immunohistochemistry results showed that endostatin-loaded PAMAM reduced the microvessel density 3.8 ± 2.4 especially in HD PAMAM-ES group in the lesion (P<0.05).Conclusion. Endostatin-loaded PAMAM inhibits the development of endometriosis through an antiangiogenic mechanism and can be observed through the noninvasive endometriosis model.

After committing an error, participants tend to perform more slowly. This phenomenon is called post-error slowing (PES). Although previous studies have explored the PES effect in the context of observed errors, the issue as to whether the slowing effect generalizes across tasksets remains unclear. Further, the generation mechanisms of PES following observed errors must be examined. To address the above issues, we employed an observation-execution task in three experiments. During each trial, participants were required to mentally observe the outcomes of their partners in the observation task and then to perform their own key-press according to the mapping rules in the execution task. In Experiment 1, the same tasksets were utilized in the observation task and the execution task, and three error rate conditions (20%, 50% and 80%) were established in the observation task. The results revealed that the PES effect after observed errors was obtained in all three error rate conditions, replicating and extending previous studies. In Experiment 2, distinct stimuli and response rules were utilized in the observation task and the execution task. The result pattern was the same as that in Experiment 1, suggesting that the PES effect after observed errors was a generic adjustment process. In Experiment 3, the response deadline was shortened in the execution task to rule out the ceiling effect, and two error rate conditions (50% and 80%) were established in the observation task. The PES effect after observed errors was still obtained in the 50% and 80% error rate conditions. However, the accuracy in the post-observed error trials was comparable to that in the post-observed correct trials, suggesting that the slowing effect and improved accuracy did not rely on the same underlying mechanism. Current findings indicate that the occurrence of PES after observed errors is not dependent on the probability of observed errors, consistent with the assumption of cognitive control account. Moreover, the PES effect appears across tasksets with distinct stimuli and response rules in the context of observed errors, reflecting a generic process. Additionally, the slowing effect and improved accuracy in the post-observed error trial do not occur together, suggesting that they are independent behavioral adjustments in the context of observed errors.

The prefrontal cortex is responsible for emotional conflict resolution and this control mechanism is affected by the emotional valence of distracting stimuli. In the present study, we investigated effects of negative and positive stimuli on emotional conflict control using a face-word Stroop task in combination with functional brain imaging. Emotional conflict was absent in the negative face context, in accordance with the null activation observed in areas regarding emotional face processing (fusiform face area, middle temporal/occipital gyrus). Importantly, these visual areas negatively coupled with the dorsolateral prefrontal cortex (DLPFC). However, the significant emotional conflict was observed in the positive face context, this effect was accompanied by activation in areas associated with emotional face processing and the default mode network (DMN), here, DLPFC mainly negatively coupled with DMN, rather than visual areas. These results suggested that the conflict control mechanism exerted differently between negative faces and positive faces, it implemented more efficiently in the negative face condition, whereas it is more devoted to inhibiting internal interference in the positive face condition. This study thus provides a plausible mechanism of emotional conflict resolution that the rapid pathway for negative emotion processing efficiently triggers control mechanisms to preventively resolve emotional conflict.

The perceptual load theory in selective attention literature proposes that the interference from task-irrelevant distractor is eliminated when perceptual capacity is fully consumed by task-relevant information. However, the biased competition model suggests that the contents of working memory (WM) can guide attentional selection automatically, even when this guidance is detrimental to visual search. An intriguing but unsolved question is what will happen when selective attention is influenced by both perceptual load and WM guidance. To study this issue, behavioral performances and event-related potentials (ERPs) were recorded when participants were presented with a cue to either identify or hold in memory and had to perform a visual search task subsequently, under conditions of low or high perceptual load. Behavioural data showed that high perceptual load eliminated the attentional capture by WM. The ERP results revealed an obvious WM guidance effect in P1 component with invalid trials eliciting larger P1 than neutral trials, regardless of the level of perceptual load. The interaction between perceptual load and WM guidance was significant for the posterior N1 component. The memory guidance effect on N1 was eliminated by high perceptual load. Standardized Low Resolution Electrical Tomography Analysis (sLORETA) showed that the WM guidance effect and the perceptual load effect on attention can be localized into the occipital area and parietal lobe, respectively. Merely identifying the cue produced no effect on the P1 or N1 component. These results suggest that in selective attention, the information held in WM could capture attention at the early stage of visual processing in the occipital cortex. Interestingly, this initial capture of attention by WM could be modulated by the level of perceptual load and the parietal lobe mediates target selection at the discrimination stage.

Switch costs have been constantly found asymmetrical when switching between two tasks of unequal dominance. We used a combined Stroop-task-switching paradigm and recorded electroencephalographic (EEG) signals to explore the neural mechanism underlying the phenomenon of asymmetrical switch costs. The results revealed that a fronto-central N2 component demonstrated greater negativity in word switch (cW) trials relative to word repeat (wW) trials and both First P3 and P3b components over the parieto-central region exhibited greater positivity in color switch (wC) trials relative to color repeat (cC) trials, whereas a contrasting switch-related fronto-central SP effect was found to have an opposite pattern for each task. Moreover, the time-frequency analysis showed a right-frontal lower alpha band (9-11 Hz) modulation in the word task, whereas a fronto-central upper alpha band (11-13 Hz) modulation was exclusively found in the color task. These results provide evidence for dissociable neural processes, which are related to inhibitory control and endogenous control, contributing to the generation of asymmetrical switch costs.

Objectives To establish red fluorescent human endometriosis lesions in a nude mouse model and dynamically and non-invasively to compare intraperitoneal and subcutaneous injection models. Study design Primary cultures of endometrial stromal cells (ESCs) and epithelial cells (EECs) isolated from 24 patients with a normal uterine cavity were transfected with 2.5 × 10 8 (Group 1) and 1.25 × 10 8 (Group 2) plaque-forming units (PFU) of adenovirus encoding red fluorescent protein (Ad-RFP). Transfection efficiencies, fluorescence intensity and apoptosis rate of the two types of cells were compared in vitro. A mixture of 2.5 × 10 8 PFU Ad-RFP-infected approximately 400 EECs cell mass and 2 × 10 6 ESCs for 36 h was injected individually into 24 female nude mice subcutaneously (Group A) or intraperitoneally (Group B). From Day 5 after injection, an in vivo imaging system (IVIS) was used to non-invasively observe and compare the lesions of the two groups every week until Day 33. Specifically, the fluorescent intensity, positive rates, persistence time and lesion weight in the implanted human endometriosis lesions were compared. A parametric Student's t -test and two-way analysis of variance were used for statistical analysis. Results Compared with 1.25 × 10 8 PFU RFP, a titre of 2.5 × 10 8 PFU RFP ESCs and EECs incubated for 36 h exhibited higher transfection efficiencies and higher fluorescence intensities in vitro. In vivo imaging of the fluorescent human endometriosis lesions originating from an RFP titre of 2.5 × 10 8 PFU showed that the intensity and lesion weight in Group A were significantly higher than in Group B. However, the two groups had the same RFP-positive rates and fluorescence persistence. The structure of each lesion was evaluated by immunohistochemistry to confirm its human endometrial origin. Conclusions The red fluorescent human endometriosis model established by subcutaneously injecting 2.5 × 10 8 PFU RFP-transfected stromal cells and epithelial cells into nude mice had a higher fluorescent positive rate from Day 5, higher intensity and weight but the same persistence as the intraperitoneal injection model.