Epidemiological and CBCT characterizations of odontomas: A retrospective study of 87,590 subjects.

OBJECTIVES: This study aimed to assess the epidemiological and three-dimensional (3D) radiological characterizations of odontomas, as well as the spatial relationship between odontomas and gubernaculum tracts (GT). MATERIALS AND METHODS: We retrieved the cone-beam computed tomography (CBCT) data of 87,590 patients. Dentition, location, type, diameter of the odontomas, width of the dental follicle (DF), the spatial relationship between the odontoma and GT, and the influence on adjacent teeth were evaluated. RESULTS: Significant differences were found in age, dentition, location, Max/Min diameter, width of DF, impaction, retention, and root bending of adjacent teeth among different spatial relationships between the odontoma and GT (all p < 0.05), as well as in age, type and size, absence, impaction, malposition, and retention of adjacent teeth among different locations of odontomas (all p < 0.05). Compared to the odontomas without impaction, those with impaction had larger diameter (p < 0.05 in all directions). This statistically significant association was consistent for odontomas with malposition, while no similar result was observed in the maximum diameter. CONCLUSION: Our findings provide the preliminary data for clinicians to comprehensively understand the incidence, radiographic characterizations and symptoms of odontoma in Chinese population.

Association of formaldehyde concentration with depression risk in US adults: a population-based epidemiology study.

The association of formaldehyde exposure with depression remains unknown. We used the data from National Health and Nutrition Examination Survey (NHANES) 2015-2016 to evaluate the association between formaldehyde exposure and depression. Multivariable logistic regressions and restricted cubic spline (RCS) were implemented to examine the association between formaldehyde exposure and depression. A total of 1336 participants were included in the analysis, of which 110 (8.23%) participants were depressed. After adjusting for confounders, a significant association between formaldehyde exposure and depression (OR = 1.01, 95% CI: 1.00-1.02, P = 0.043) was observed. The RCS plot showed a positive association in a linear manner (PNonlinear = 0.109), and the risk began to rise rapidly with concentrations above 129.37 nmol/g HB. The positive association remained in participants with high-intensity physical activity (OR = 1.08, 95% CI: 1.02-1.13, P = 0.003), but not in participants with other physical activities. Moreover, we constructed a novel nomogram to easily estimate the individual-specific probabilities of depression. In conclusion, formaldehyde exposure was associated with an elevated risk of depression, and the effect exhibited differences in participants with different levels of physical activity.

Serum Concentrations of Benzaldehyde, Isopentanaldehyde and Sex Hormones: Evidence from the National Health and Nutrition Examination Survey.

Exposure to environmental chemicals could disturb the balance of sex hormones. However, the studies on Benzaldehyde, Isopentanaldehyde exposure and sex hormones are still limited. Based on the data of 1064 participants in the National Health and Nutrition Examination Survey (NHANES), we used the linear regression model and restricted cubic spline (RCS) model to evaluate the associations of Benzaldehyde/Isopentanaldehyde exposure with testosterone (TT), estradiol (E2), sex hormone binding globulin (SHBG), free androgen index (FAI) and the ratio of TT to E2 (TT/E2). A ln-unit increase in Benzaldehyde was associated with lower TT (ß = -0.048, P = 0.030) and E2 (ß = -0.094, P = 0.046) in all participants. After further adjustment for menopausal status, Benzaldehyde was negatively associated with E2 (ß = -0.174, P = 0.045) in females. The interaction between Benzaldehyde and gender was significant (Pinter = 0.031). However, Isopentanaldehyde showed a positive association with SHBG and TT/E2 in all participants (all P < 0.05). The positive associations of Isopentanaldehyde with TT, SHBG and TT/E2 were found in males but not in females. RCS plots illustrated the linear associations of Benzaldehyde with E2 (Pnon-linear = 0.05) in females and Isopentanaldehyde with TT (Pnon-linear = 0.07) and TT/E2 (Pnon-linear = 0.350) in males. The non-linear relationships were identified between Isopentanaldehyde and SHBG in males (Pnon-linear = 0.035). Our findings indicated the effects of Benzaldehyde and Isopentanaldehyde exposure on sex hormones, and the effects had the gender specificity. Cohort studies and high-quality in vitro and in vivo experiments are needed to confirm the specific effects and uncover the underlying mechanisms.

Peptidomics analysis of human breast milk from women with postpartum depression reveals its potential pathogenesis.

BACKGROUND: Postpartum depression (PPD) is a prevalent psychiatric disorder during the postnatal period, and it exerts adverse impacts not only on mothers but also on infants, impairing the well-being of the whole family. However, the role of peptides in the breast milk of mothers with PPD has not been studied. The purpose of this study was to unveil the peptidomic profile of PPD from breast milk samples. METHODS: We performed comparative peptidomic profiling of human breast milk from PPD and control mothers using liquid chromatography-tandem mass spectrometry technology with iTRAQ-8 labelling. GO and KEGG pathway analyses of precursor proteins were used to predict the underlying biological functions of differentially expressed peptides (DEPs). Ingenuity Pathway Analysis (IPA) was further performed to explore the interactions and involved pathways of DEPs. RESULTS: A total of 294 peptides from 62 precursor proteins were identified to be differentially expressed in the breast milk of PPD mothers compared with the control group. Bioinformatics analysis predicted that these DEPs were associated with ECM-receptor interaction, neuroactive ligand-receptor interaction, cell adhesion molecule binding and oxidative stress in macrophages. These results indicate that DEPs from human breast milk may play a part in PPD and become promising noninvasive biomarkers.

Cardiac magnetic resonance feature tracking myocardial strain analysis in suspected acute myocarditis: diagnostic value and association with severity of myocardial injury.

BACKGROUND: Albeit that cardiac magnetic resonance feature tracking (CMR-FT) has enabled quantitative assessment of global myocardial strain in the diagnosis of suspected acute myocarditis, the cardiac segmental dysfunction remains understudied. The aim of the present study was using CMR-FT to assess the global and segmental dysfunction of the myocardium for diagnosis of suspected acute myocarditis. METHODS: Forty-seven patients with suspected acute myocarditis (divided into impaired and preserved left ventricular ejection fraction [LVEF] groups) and 39 healthy controls (HCs) were studied. A total of 752 segments were divided into three subgroups, including segments with non-involvement (SNi), segments with edema (SE), and segments with both edema and late gadolinium enhancement (SE+LGE). 272 healthy segments served as the control group (SHCs). RESULTS: Compared with HCs, patients with preserved LVEF showed impaired global circumferential strain (GCS) and global longitudinal strain (GLS). Segmental strain analysis showed that the peak radial strain (PRS), peak circumferential strain (PCS), and peak longitudinal strain (PLS) values significantly reduced in SE+LGE compared with SHCs, SNi, SE. PCS significantly reduced in SNi (-15.3 ± 5.8% vs. -20.3 ± 6.4%, p < 0.001) and SE (-15.2 ± 5.6% vs. -20.3 ± 6.4%, p < 0.001), compared with SHCs. The area under the curve (AUC) values of GLS (0.723) and GCS (0.710) were higher than that of global peak radial strain (0.657) in the diagnosis of acute myocarditis, but the difference was not statistically significant. Adding the Lake Louise Criteria to the model resulted in a further increase in diagnostic performance. CONCLUSIONS: Global and segmental myocardial strain were impaired in patients with suspected acute myocarditis, even in the edema or relatively non-involved regions. CMR-FT may serve as an incremental tool for assessment of cardiac dysfunction and provide important additional imaging-evidence for distinguishing the different severity of myocardial injury in myocarditis.

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most fatal gynaecological malignancy and has a poor prognosis. Glycosylation, the biosynthetic process that depends on specific glycosyltransferases (GTs), has recently attracted increasing importance due to the vital role it plays in cancer. In this study, we aimed to determine whether OC patients could be stratified by glycosyltransferase gene profiles to better predict the prognosis and efficiency of immune checkpoint blockade therapies (ICBs). METHODS: We retrieved transcriptome data across 420 OC and 88 normal tissue samples using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively. An external validation dataset containing 185 OC samples was downloaded from the Gene Expression Omnibus (GEO) database. Knockdown and pathway prediction of B4GALT5 were conducted to investigate the function and mechanism of B4GALT5 in OC proliferation, migration and invasion. RESULTS: A total of 50 differentially expressed GT genes were identified between OC and normal ovarian tissues. Two clusters were stratified by operating consensus clustering, but no significant prognostic value was observed. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 6-gene signature was built that classified OC patients in the TCGA cohort into a low- or high-risk group. Patients with high scores had a worse prognosis than those with low scores. This risk signature was further validated in an external GEO dataset. Furthermore, the risk score was an independent risk predictor, and a nomogram was created to improve the accuracy of prognostic classification. Notably, the low-risk OC patients exhibited a higher degree of antitumor immune cell infiltration and a superior response to ICBs. B4GALT5, one of six hub genes, was identified as a regulator of proliferation, migration and invasion in OC. CONCLUSION: Taken together, we established a reliable GT-gene-based signature to predict prognosis, immune status and identify OC patients who would benefit from ICBs. GT genes might be a promising biomarker for OC progression and a potential therapeutic target for OC.

The clinical characteristics of Chinese elderly patients with different durations of type 2 diabetes mellitus.

Aims: To explore the clinical characteristics among elderly (aged ≥60 years) patients with type 2 diabetes (T2DM) of different durations. Methods: Clinical characteristics were investigated in 3840 elderly T2DM patients according to their different durations of diabetes (< 1 year, 1~5 years, 5~10 years, and ≥ 10 years). Kruskal-Wallis and Dunn tests were used to assess the differences among groups for continuous variables. The chi-square and post hoc tests were carried out for dichotomous variables. The logistic regression was adopted to investigate the relationships between various durations of diabetes and the control rates of achieving the control targets for T2DM as well as diabetic vascular complications. Results: There were 972, 896, 875 and 1097 patients with a duration of diabetes of <1, 1~5, 5~10 and ≥10 years, respectively. In logistic regression models adjusted for age, sex, education, BMI, smoking and family history of diabetes, elderly T2DM patients with a duration of diabetes of ≥10 years were more likely to reach the comprehensive control targets for TC (ORTC = 1.36, 95% CI =1.14-1.63), LDL-C (ORLDL-C = 1.39, 95% CI =1.17-1.66), TG (ORTG = 1.76, 95% CI =1.46-2.12) and BMI (ORBMI = 1.82, 95% CI =1.52-2.18). Elderly T2DM patients with a duration of diabetes of 1~5 years were more likely to achieve the HbA1c control target (ORHbA1c = 1.92, 95% CI = 1.59-2.31) than elderly T2DM patients with a duration of diabetes of <1 year. Furthermore, in elderly T2DM patients with a duration of diabetes of 5~10 years or ≥ 10 years, the duration of diabetes was positively associated with diabetic macrovascular complications (coronary heart disease and peripheral artery disease). In elderly T2DM patients with a duration of diabetes of over 10 years, the duration of diabetes was associated with diabetes kidney disease (all P < 0.05). Conclusions: It is worth noting that the clinical characteristics of elderly patients with type 2 diabetes in different durations of diabetes are different.

A Review of Microsurgical Resection of Recurrent Laryngeal Neurilemmoma Under Nerve Monitoring.

BACKGROUND: Laryngeal neurilemmoma, especially recurrent laryngeal neurilemmoma, is a rare neural sheath tumor in head and neck. The most common symptom of laryngeal neurilemmoma is hoarseness or dysphonia, followed by dysphagia, dyspnea, and foreign body sensation. At present, surgical resection is the most effective treatment for this kind of tumor, thus making how to remove it become the most concerned problem of surgeons. CASE PRESENTATION: On February 18, 2021, a 64-year-old male presented to our clinic with recurrent sore throat and intermittent hoarseness for 3 years. The results of electronic laryngoscope and magnetic resonance imaging showed a 25×10×21 mm well-defined tumor in the left pyriform sinus without laryngeal cartilage destruction and enlarged lymph nodes. After the initial diagnosis of recurrent laryngeal neurilemmoma, to preserve the continuity of recurrent laryngeal nerve as much as possible, the authors determine to perform anatomical resection of recurrent laryngeal neurilemmoma with operating microscope under the monitoring of recurrent laryngeal nerve function. Finally, the patient recovered completely from hoarseness during postoperative follow-up. CONCLUSION: A complete diagnosis and treatment process of recurrent laryngeal neurilemmoma was presented by the case. Particularly, it shows the application of recurrent laryngeal nerve monitoring in the operation helps to protect the continuity of the recurrent laryngeal nerve, which lays a anatomical bases for the follow-up nerve repair.

The Association Between Hypertensive Disorders in Pregnancy and the Risk of Developing Chronic Hypertension.

Objective: This meta-analysis comprehensively evaluated the association between hypertensive disorders in pregnancy (HDP) and the risk of developing chronic hypertension and the associations between specific types of HDP, including preeclampsia (PE) and gestational hypertension (GH), and the risk of developing chronic hypertension. Design: Systematic review and meta-analysis. Data Sources: The PubMed, Embase and Cochrane Library databases were searched from inception to August 20, 2021. Methods: Depending on heterogeneity, the combined odds ratio (OR) of the 95% confidence interval (CI) was obtained with a random-effects or fixed-effects model. We used meta-regression analysis to explore the sources of heterogeneity. We analyzed the OR value after adjusting for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors. Additionally, we evaluated the results of the subgroup analysis by the year of publication (< 2016, ≥ 2016), study design, sample size (< 500, ≥ 500), region (North and South America, Europe, and other regions) and NOS score (< 7, ≥ 7). Results: Our systematic review and meta-analysis comprehensively explored the relationships between HDP, GH, and PE and chronic hypertension. Twenty-one articles that included 634,293 patients were included. The results of this systematic review and meta-analysis suggested that women with a history of HDP are almost 3.6 times more likely to develop chronic hypertension than those without a history of HDP, women with a history of GH are almost 6.2 times more likely to develop chronic hypertension than those without a history of GH, and women with a history of PE are almost 3.2 times more likely to develop chronic hypertension than those without a history of PE. In addition, we further calculated the probability of developing chronic hypertension among patients with HDP or PE after adjusting for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors. The results suggested that women with a history of HDP are almost 2.47 times more likely to develop chronic hypertension than those without a history of HDP and that women with a history of PE are almost 3.78 times more likely to develop chronic hypertension than those without a history of PE. People in Asian countries are more likely to develop chronic hypertension after HDP or PE, while American people are not at high relative risk. Conclusion: These findings suggest that HDP, GH, and PE increase the likelihood of developing chronic hypertension. After adjustment for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors, patients with HDP or PE were still more likely to develop chronic hypertension. HDP may be a risk factor for chronic hypertension, independent of other risk factors. GH and PE, as types of HDP, may also be risk factors for chronic hypertension. Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD42021238599].

Association of dissection features and primary collateral circulation with ischemic stroke in patients with spontaneous internal carotid artery dissection: evaluated using vessel wall-MRI and MRA.

OBJECTIVE: To study the ischemic stroke risk factors in spontaneous internal carotid artery dissection (ICAD) patients via analyzing the dissection features and primary collateral circulation using vessel wall-MRI and magnetic resonance angiography. METHODS: ICAD patients who had undergone VW-MRI were included in this study. A total of 36 patients were included and divided into ICAD stroke (N = 23) and non-stroke (N = 13) group. Dissection imaging features [intramural hematoma (IMH), length of IMH, intimal flap, double lumen, intraluminal thrombus, degree of stenosis] and primary collateral status were analyzed. The primary collateral score (0-4) was evaluated based on presence of anterior communicating and ipsilateral anterior cerebral artery A1 segment (0-2) and ipsilateral posterior communicating artery (0-2). RESULTS: There were no significant differences in dissection imaging features such as presence of double lumen, intimal flap, IMH, length of IMH and intraluminal thrombus between the two groups. Degree of stenosis and primary collateral score showed significant differences between the two groups. CONCLUSION: Both the poor primary collateral circulation and severe stenosis may play an important role in occurrence of ischemic stroke for spontaneous ICAD patients and good primary collateral circulation can help to reduce the incidence of infarction. ADVANCES IN KNOWLEDGE: ICAD is one of the major causes of ischemic stroke. Early evaluation of the status of the Circle of Willis in ICAD patients by MRI may help to make treatment strategies and improve clinical outcome.

Exploration and preliminary clinical investigation of an adhesive approach for primary tooth restoration.

The current study aims to investigate a suitable adhesive for primary tooth enamel. Shear bond strength (SBS) of primary teeth and the length of resin protrusion were analyzed using one-way ANOVA with Bonferroni multiple comparison tests after etching with 35% H 3PO 4. SBS and marginal microleakage tests were conducted with Single Bond Universal (SBU)/Single Bond 2 (SB2) adhesives with or without pre-etching using a nonparametric Kruskal-Wallis test. Clinical investigations were performed to validate the adhesive for primary teeth restoration using Chi-square tests. Results showed that the SBS and length of resin protrusion increased significantly with the etching time. Teeth in the SBU with 35% H 3PO 4 pre-etching groups had higher bond strength and lower marginal microleakage than those in the SB2 groups. Mixed fractures were more common in the 35% H 3PO 4 etched 30 s + SB2/SBU groups. Clinical investigations showed significant differences between the two groups in cumulative retention rates at the 6-, 12- and 18-month follow-up evaluations, as well as in marginal adaptation, discoloration, and secondary caries at the 12- and 18-month follow-up assessments. Together, pre-etching primary teeth enamel for 30 s before SBU treatment improved clinical composite resin restoration, which can provide a suitable approach for restoration of primary teeth.

The COL-4A1 polypeptide destroy endothelial cells through the TGF-ß/PI3K/AKT pathway.

Preeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed to explore the correlation between the novel polypeptide COL-4A1 and PE, and to identify the underlying mechanism by which this polypeptide may function and to explore new therapeutic targets for PE. A rat model of PE was established and used to verify the function of the polypeptide COL-4A1 in vivo. Additionally, human umbilical vascular endothelial cells (HUVECs) were cultured with or without COL-4A1 and TNF-α (20 ng/ml). Cell Counting Kit-8 (CCK-8), wound-healing, Transwell and tube formation assays were used to evaluate cell proliferation, migration and angiopoiesis. RNA sequencing and mass spectrometry were conducted to explore the underlying downstream mechanism of COL-4A1. In vivo, COL-4A1 increased blood pressure and elevated the risk of fetal growth restriction (FGR) which was induced by lipopolysaccharide (LPS) in the rat model. In vitro, COL-4A1 significantly inhibited the proliferation and migration of HUVECs. After culture with COL-4A1, compared to control group the adhesive ability and level of reactive oxygen species (ROS) were enhanced and tube formation ability was decreased. Furthermore, Western blotting (WB) and pull-down assays were conducted to explore the underlying mechanism by which COL-4A1 functions, and the TGF-ß/PI3K/AKT pathway was identified as the potential pathway involved in its effects. In summary, these results revealed that the polypeptide COL-4A1 caused PE-like symptoms in cells and a rat model. Through the TGF-ß/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.

The Association Between ABO Blood Group and Preeclampsia: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis comprehensively evaluated the association between ABO blood group and the risk of preeclampsia (PE). Design: Systematic review and meta-analysis. Data sources: PubMed, Web of Science, and ScienceDirect databases from their inception to September 23, 2020. Methods: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained through random-effects and fixed-effects models according to heterogeneity. Meta-regression analysis was applied to explore the source of heterogeneity. We conducted a subgroup analysis by the publication year, study design, state, and Newcastle-Ottawa Scale (NOS) score. In addition, we calculated the rate of each ABO blood group in PE by total pooled effects. Results: A total of 12 articles with 714,153 patients were included in our analysis. Compared with people without PE (control group), the O blood group presented a lower risk of PE (OR 0.95, 95% CI 0.93-0.97). The AB (OR 1.46, 95% CI 1.12-1.91) blood group presented a higher risk. However, the total pooled OR and 95% CI for the A (OR 1.02, 95% CI 0.90-1.16) and B (OR 1.02, 95% CI 0.98-1.05) blood groups were not significant. The funnel plot and linear regression equation showed that there was no publication bias for the O, A, or B blood groups (all P > 0.05). However, the funnel plot and linear regression equation for the AB blood group were obviously asymmetric (P < 0.05), and the publication bias persisted even after the trim-and-fill method was applied (P < 0.05). Multivariable meta-regression analysis did not find a specific source of heterogeneity. The A blood group showed an association with early-onset PE (OR 0.53, 95% CI 0.33-0.83), and the other blood groups showed no significant differences. In PE, the rates of the O, A, B, and AB blood groups decreased gradually (0.39, 0.33, 0.19, 0.07). Conclusion: These findings suggest that pregnant women with AB blood group are more likely to develop PE, and more attention should be paid to AB blood group whose blood pressure is high but not sufficient to diagnose PE. Systematic Review Registration: Prospero CRD42021227930.

OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis.

Background: The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear. Methods: We identified eligible studies by searching the PubMed, Web of Science, ScienceDirect, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to determine the association of OPCML methylation with ovarian cancer risk. Meta-regression and subgroup analysis were used to assess the sources of heterogeneity. Additionally, we analyzed the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets to validate our findings. Results: Our study included 476 ovarian cancer patients and 385 controls from eight eligible studies. The pooled OR was 33.47 (95% CI = 12.43-90.16) in the cancer group vs. the control group under the random-effects model. The association was still significant in subgroups according to sample type, control type, methods, and sample sizes (all P < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's (P = 0.458) and Egger's tests (P = 0.261). We further found that OPCML methylation was related to III/IV (OR = 4.20, 95% CI = 1.59-11.14) and poorly differentiated grade (OR = 4.37; 95% CI = 1.14-16.78). Based on GSE146552 and GSE155760, we validated that three CpG sites (cg16639665, cg23236270, cg15964611) in OPCML promoter region were significantly higher in cancer tissues compared to normal tissues. However, we did not observe the associations of OPCML methylation with clinicopathological parameters and overall survival based on TCGA ovarian cancer data. Conclusion: Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.

The Cancer-Testis Long Non-coding RNA PCAT6 Facilitates the Malignant Phenotype of Ovarian Cancer by Sponging miR-143-3p.

Background: It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC. Methods: The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan-Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC. Results: PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-ß-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion. Conclusions: Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.

A human ß-casein-derived peptide BCCY-1 modulates the innate immune response.

In this study, we report a novel peptide corresponding to the sequence of human ß-casein (named BCCY-1), which was identified in our previous peptidome analysis of human milk and has great immunomodulatory activity. The results revealed that peptide BCCY-1, but not the scrambled version, enhanced monocyte migration without obvious toxicities. This selective effect was mediated via increased production of chemokines by peptide stimulated monocytes. Moreover, BCCY-1 exerted its modulatory effects by activating nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling. The abundances of peptide BCCY-1 and the peptides partially encompassing its fragment were found to be lower in preterm milk than in term milk. Our study may lead to new insights into the immunoregulatory effects of casein-derived peptides and facilitate the discovery of novel peptide-based food and pharmaceutical products.

The Association Between Cadmium Exposure and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: Several studies have evaluated the association of cadmium exposure with the risk of gestational diabetes mellitus (GDM). However, the findings among these studies have been inconsistent. To further investigate the relationship, we carried out a meta-analysis to clarify the relationship between cadmium exposure and GDM risk. METHODS: Five databases (Scopus, PubMed, Web of Science, Cochrane, and CNKI) were searched for eligible studies until September 09, 2021. The quality of eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale (NOS). The summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by random-effects models due to high heterogeneity. Sensitivity analysis was performed to explore the robustness of the results. Publication bias was evaluated by Egger's test and Begg's test. We also conducted meta-regression analysis and subgroup analysis to assess the potential sources of heterogeneity. RESULTS: A total of 10 studies with 32,000 participants related to our issue were included. Comparing the highest vs. lowest categories of cadmium exposure, no significant association was observed between cadmium exposure and the risk of GDM (OR = 1.16, 95% CI = 0.92-1.46, and P = 0.206). No publication bias was found in Begg's and Egger's tests (all P > 0.05). Meta-regression suggested that publication year was the potentially heterogeneous source (P = 0.034). Subgroup analysis of publication year showed that the OR of studies before the year of 2016 was 4.05 (95% CI = 1.87-8.76, P < 0.001), and prospective cohort studies showed a borderline increased GDM risk (OR = 1.15, 95% CI = 0.99-1.33, and P = 0.061). CONCLUSION: Our results indicated no significant association between cadmium exposure and GDM risk. Further high-quality prospective studies, especially those using standard analytic methods for cadmium exposure, are warranted to confirm the results.

A novel peptide relieves endothelial cell dysfunction in preeclampsia by regulating the PI3K/mTOR/HIF1α pathway.

Preeclampsia (PE) is a pregnancy­specific complication characterized by hypertension and proteinuria, and it is one of the primary global causes of maternal and perinatal mortality. Poor remodeling of placental arteries and endothelial dysfunction serve important roles in the pathogenesis of PE. Peptide derived from complement C4 A chain (PDCC4) was identified in our previous peptidome analysis of serum from patients with PE. The present study aimed to investigate the effect of PDCC4 on endothelial dysfunction in PE. TNF­α stimulated HUVECs were employed to mimic endothelial dysfunction in PE, and Cell Counting Kit 8 assay, wound healing assay, tube formation assay, RNA­sequencing (seq) and western blot analysis were performed using HUVECs. Moreover, an in vivo model of PE was established using pregnant rats treated with lipopolysaccharide (LPS), and blood pressure monitoring, histopathological examination, ELISA and immunohistochemistry were performed on rats. It was found that TNF­α impaired proliferation, migration and tube formation of HUVECs, but pretreatment with PDCC4 moderated these effects. RNA­seq and western blotting demonstrated that the PI3K/mTOR/HIF1α signaling pathway was activated by PDCC4, and a selective PI3K inhibitor reversed the protective function of PDCC4 on TNF­α stimulated HUVECs. Additionally, PDCC4 alleviated hypertension, histopathological changes of placenta and kidney and the expression levels of endothelial injury markers and inflammatory cytokines induced by LPS in rats. These results suggested that PDCC4 relieved endothelial dysfunction in PE via PI3K/mTOR/HIF1α signaling pathway and may be a potential therapy for PE.

Profiling Analysis Reveals the Crucial Role of the Endogenous Peptides in Bladder Cancer Progression.

BACKGROUND: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study. METHODS: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases. RESULTS: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, P < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that 45HFNPRFNAHGDAN 57 derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer. CONCLUSION: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.

Neonatal Adverse Outcomes of Induction and Expectant Management in Fetal Growth Restriction: A Systematic Review and Meta-Analysis.

Background and Objective: Fetal growth restriction (FGR) is a pathological condition in which the fetus cannot reach its expected growth potential. When it is diagnosed as a suspected FGR, it remains an unsolved problem whether to direct induction or continue expectant management. To effectively reduce the incidence of neonatal adverse outcomes, we aimed to evaluate whether either method was associated with a lower incidence of neonatal adverse outcomes. Methods: We searched the relevant literature through the PubMed, Web of Science, and Cochrane Library from inception to January 10, 2020. We defined induction as the experimental group and expectant management as the control group. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models owing to heterogeneity. Furthermore, we conducted a sensitivity analysis to explore the robustness of the included literature. We used the Newcastle-Ottawa scale (NOS) to evaluate the quality of the available studies. We applied the funnel plot to describe the publication bias. Additionally, subgroup analysis based on the study method, sample size, area, NOS score, Apgar score <7 at 5 min, definition of suspected FGR, severity, and neonatal adverse outcomes were performed to further evaluate the differences between the induction and expectant management. Results: Our study included a total of eight articles with 6,706 patients, which consisted of four randomized controlled trials (RCTs), three retrospective cohort studies, and one prospective cohort study. The total pooled OR and 95% CI between the induction group and the expected management group was 1.38 (95% CI, 0.84-2.28) in the random model. The heterogeneity was I 2 = 84%, P < 0.01. The sensitivity analysis showed that the neonatal adverse outcomes of induction vs. expectant management still presented similar outcomes after omitting of any one of these studies. The funnel plot and linear regression equation showed that there was no publication bias in our study (P = 0.75). Subgroup analysis showed that induction increased the neonatal adverse outcome risks of hypoglycemia and respiratory insufficiency (ORneonatal hypoglycaemia = 8.76, 95% CI: 2.57-29.90; ORrespiratory insufficiency = 1.74, 95% CI: 1.35-2.24, respectively). However, no significant differences were observed based on the other subgroups (all P > 0.05). Conclusion: Regardless of induction or expectant management of a suspected FGR, the neonatal adverse outcomes showed no obvious differences. More studies should be conducted and confounding factors should be taken into consideration to elucidate the differential outcomes of the two approaches for suspected FGR.