PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection.

The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People's Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical-vaginal lesions, especially for HPV other than 16/18 genotypes.

The role of Sertoli cells-secreted factors in different stages of germ cells development in mice exposed to BDE-209.

Decabromodiphenyl ether (BDE-209), a frequently used brominated flame retardant, readily enters the environment and is difficult to degrade with bioaccumulation. BDE-209 could cause male reproductive toxicity, but the regulatory functions of Sertoli cells-secreted factors remain uncertain. In present study, male mice were treated with 75 mg/kg BDE-209 and then stopped exposure for 50 days. Exogenous Glial cell line-derived neurotrophic factor (GDNF), a Sertoli cell-secreted factor, was injected into testes of mice treated with BDE-209 for 50 days to explore the role of GDNF in BDE-209-induced reproductive toxicity. The mouse spermatogonia cell line GC-1 spg was used in vitro to further verify regulatory effects of Sertoli cells-secreted factors on meiotic initiation. The results showed that BDE-209 inhibited expressions of the self-renewal pathway GFRα-1/RAS/ERK1/2 in spermatogonial stem cells (SSCs), and reduced expressions of spermatogonia proliferation-related pathway NRG3/ERBB4 and meiosis initiation factor Stra8. Furthermore, BDE-209 decreased the levels of both GDNF and retinoic acid (RA) secreted by Sertoli cells in testes. Importantly, the alterations of above indicators induced by BDE-209 did not recover after 50-day recovery period. After exogenous GDNF injection, the decreased expression of GFRα-1/RAS/ERK in SSCs was reversed. However, the level of RA and expressions of NRG3/ERBB4/Stra8 were not restored. The in vitro experimental results showed that exogenous RA reversed the reductions in NRG3/ERBB4/Stra8 and ameliorated inhibition of GC-1 spg cells proliferation induced by BDE-209. These results suggested that Sertoli cells-secreted factors play roles in regulating various stages of germ cell development. Specifically, BDE-209 affected the self-renewal of SSCs by decreasing GDNF secretion resulting in the inhibition of GFRα-1/RAS/ERK pathway; BDE-209 hindered the proliferation of spermatogonia and initiation of meiosis by inhibiting the secretion of RA and preventing RA from binding to RARα, resulting in the suppression of NRG3/ERBB4/Stra8 pathway. As a consequence, spermatogenesis was compromised, leading to persistent male reproductive toxicity.

Triphenyl phosphate induces cardiotoxicity through myocardial fibrosis mediated by apoptosis and mitophagy of cardiomyocyte in mice.

Triphenyl phosphate (TPHP) is an organophosphorus flame retardant, but its cardiac toxicity has not been adequately investigated. Therefore, in the current study, the effect of TPHP on the heart and the underlying mechanism involved was evaluated. C57BL/6 J mice were administered TPHP (0, 5, and 50 mg/kg/day) for 30 days. In addition, H9c2 cells were treated with three various concentrations (0, 50, and 150 µM) of TPHP, with and without the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine or the mitochondrial fusion promoter M1. TPHP caused cardiac fibrosis and increased the levels of CK-MB and LDH in the serum. TPHP increased the levels of ROS, malondialdehyde (MDA), and decreased the level of superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px). Furthermore, TPHP caused mitochondrial damage, and induced fusion and fission disorders that contributed to mitophagy in both the heart of C57BL/6 J mice and H9c2 cells. Transcriptome analysis showed that TPHP induced up- or down-regulated expression of various genes in myocardial tissue and revealed enriched apoptosis pathways. It was also found that TPHP could remarkably increase the expression levels of Bax, cleaved Caspase-9, cleaved Caspase-3, and decreased Bcl-2, thereby causing apoptosis in H9c2 cells. Taken together, the results suggested that TPHP promoted mitophagy through mitochondria fusion dysfunction resulting from oxidative stress, leading to fibrosis by inducing myocardial apoptosis.

What can be done to protect toddlers from air pollution: Current evidence.

PROBLEM: Toddlers are more prone to exposure to widely distributed air pollution and to health damage from it. However, systematic summaries of evidence on protective behaviors against air pollution for toddlers are lacking. OBJECTIVE: To identify currently available evidence on protective behaviors against air pollution for toddlers. METHODS: The literature retrieval was performed in selected databases, limited from 2002 to 2022. Studies meeting the following criteria were included and praised: 1) clinical practice guideline, systematic review, expert consensus, recommended practice, randomized control test (RCT) or cohort study published in Chinese or English; 2) studies reporting effects of protective behaviors against air pollution on toddlers' health outcomes or providing recommendation on these behaviors. The evidence in the included studies was extracted, synthesized and graded for evidence summary. RESULTS: Studies (N = 19) were used for evidence summary development and 35 pieces of best evidence were synthesized, which were divided into three categories, including "avoiding or reducing air pollution generation", "removing existing air pollution", and "avoiding or reducing exposure to existing air pollution". CONCLUSIONS: More evidence is needed to identify protective measures against outdoor air pollution and tobacco smoke. Research in the future should focus on the safety, effectiveness and feasibility of universal measures implemented in toddlers, and try to develop protective measures specific to toddlers which highlight their special nature. IMPLICATIONS: The results of this study can help pediatric nurses provide individualized advice and assistance for toddlers and their families, and conduct research on the effectiveness of toddler-targeting protective behaviors more efficiently.

A novel upregulated hsa_circ_0032746 regulates the oncogenesis of esophageal squamous cell carcinoma by regulating miR-4270/MCM3 axis.

INTRODUCTION: Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3'- and 5'- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. MATERIALS AND METHODS: 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis  predicted binding affinity of circRNA/miRNA/mRNA axis. RESULTS: After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. CONCLUSION: We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.

Digital cholangioscopy-assisted, direct visualization-guided, radiation-free, endoscopic retrograde intervention for cholelithiasis: technical feasibility, efficacy, and safety.

BACKGROUND: Nonradiation, digital cholangioscope (DCS)-assisted endoscopic intervention for cholelithiasis has not been widely performed. For this study, we aimed to report the feasibility, efficacy, and safety of an established DCS-guided lithotomy procedure. METHODS: Data relating to biliary exploration, stone clearance, adverse events, and follow-up were obtained from 289 patients. The choledocholithiasis-related outcomes via the DCS-guided procedure were subsequently compared to those via conventional endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Biliary access was achieved in 285 patients. The technical success rate for the exploration of the common bile duct, the cystic stump, the hilar ducts, and secondary radicals was 100%. Moreover, the success rates were 98.4%, 61.7%, and 20.7%, for the exploration of the cystic duct, complete cystic duct, and gallbladder, respectively. Suspicious or confirmed suppurative cholecystitis, cholesterol polyps, and hyperplastic polyps were detected in 42, 23, and 5 patients, respectively. Stone clearance was achieved in one session in 285 (100%), 11 (100%), 13 (100%), 7 (100%), 6 (100%), and 3 (14.3%) patients with choledocholithiasis and hepatolithiasis, cystic duct stump stones, nondiffuse located intrahepatic lithiasis, a single cystic duct stone, a single gallbladder stone, and diffuse located intrahepatic lithiasis, respectively. Complete stone clearance for diffuse intrahepatic lithiasis was achieved in 19 (90.5%) patients, and fractioned re-lithotomy was performed in 16 (76.2%) patients. One patient developed mild acute cholangitis, and 12 developed mild pancreatitis. Stones recurred in one patient. Compared with conventional ERCP, DCS-guided lithotomy has the advantages of clearing difficult-to-treat choledocholithiasis and revealing concomitant biliary lesions, and this technique has fewer complications and a decreased risk of stone recurrence. CONCLUSIONS: The technical profile, efficacy, and safety of nonradiation-guided and DCS-guided lithotomy are shown in this study. We provide a feasible modality for the endoscopic removal of cholelithiasis.

Association between Ambient Particulate Air Pollution and Soluble Biomarkers of Endothelial Function: A Meta-Analysis.

BACKGROUND: The burden of cardiovascular diseases caused by ambient particulate air pollution is universal. An increasing number of studies have investigated the potential effects of exposure to particulate air pollution on endothelial function, which is one of the important mechanisms for the onset and development of cardiovascular disease. However, no previous study has conducted a summary analysis of the potential effects of particulate air pollution on endothelial function. OBJECTIVES: To summarize the evidence for the potential effects of short-term exposure to ambient particulate air pollution on endothelial function based on existing studies. METHODS: A systematic literature search on the relationship between ambient particulate air pollution and biomarkers of endothelial function including endothelin-1 (ET-1), E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was conducted in PubMed, Scopus, EMBASE, and Web of Science up to 20 May 2023. Subsequently, a meta-analysis was conducted using a random effects model. RESULTS: A total of 18 studies were included in this meta-analysis. A 10 µg/m3 increase in short-term exposure to ambient PM2.5 was associated with a 1.55% (95% CI: 0.89%, 2.22%) increase in ICAM-1 and a 1.97% (95% CI: 0.86%, 3.08%) increase in VCAM-1. The associations of ET-1 (0.22%, 95% CI: -4.94%, 5.65%) and E-selectin (3.21%, 95% CI: -0.90% 7.49%) with short-term exposure to ambient PM2.5 were statistically insignificant. CONCLUSION: Short-term exposure to ambient PM2.5 pollution may significantly increase the levels of typical markers of endothelial function, including ICAM-1 and VCAM-1, suggesting potential endothelial dysfunction following ambient air pollution exposure.

Diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum: a multicentre cohort study with a minimum follow-up of 3 years.

OBJECTIVE: To evaluate the medium- and long-term outcomes of diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum. METHODS: Consecutive patients with symptomatic oesophageal diverticulum who underwent D-POEM from 1st May 2016 to 1st April 2020 in 6 centres were extracted and researched. Symptoms assessed by the modified Eckardt score were registered pre- and post-D-POEM at 1, 6, 12, 24 and 36 months. RESULTS: A total of 34 patients with Zenker's diverticulum (ZD, n = 12), mid-oesophageal diverticulum (MED, n = 12), and epiphrenic diverticulum (ED, n = 10) were included. Complete septotomy was achieved in a mean of 39.15 min, with 100% technical success. No severe intraoperative or postoperative complications were observed. Five patients exhibited subcutaneous emphysema, while 1 had mucosal injury. The mean Eckardt score was 8.59 preoperatively and 2.56 at 1 month, 2.09 at 6 months, 2.21 at 12 months, 2.15 at 24 months, and 2.21 at 36 months postoperatively. The total clinical success rates at 1, 6, 12, 24 and 36 months postoperatively were 97.1%, 97.1%, 94.1%, 91.2%, and 88.2%, respectively. With a median follow-up of 47.2 months, four patients suffered symptom relapse, with a total clinical success rate of 88.2%. A long disease duration, a high Eckardt score, and coexistence of achalasia were identified as risk factors for symptomatic recurrence by multivariable Cox analysis. CONCLUSIONS: D-POEM is an effective and durable treatment for patients with symptomatic oesophageal diverticulum.

A meta-analysis-based adverse outcome pathway for the male reproductive toxicity induced by microplastics and nanoplastics in mammals.

The male reproductive toxicity of microplastics (MPs) and nanoplastics (NPs) has attracted great attention, but the latent mechanisms remain fragmented. This review performed the adverse outcome pathway (AOP) analysis and meta-analysis in 39 relevant studies, with the AOP analysis to reveal the cause-and-effect relationships of MPs/NPs-induced male reproductive toxicity and the meta-analysis to quantify the toxic effects. In the AOP framework, increased reactive oxygen species (ROS) is the molecular initiating event (MIE), which triggered several key events (KEs) at different levels. At the cellular level, the KEs included oxidative stress, mitochondrial dysfunction, sperm DNA damage, endoplasmic reticulum stress, apoptosis and autophagy of testicular cells, repressed expression of steroidogenic enzymes and steroidogenic acute regulatory protein, disrupted hypothalamic-pituitary-testicular (HPT) axis, and gut microbiota alteration. These KEs further induced the reduction of testosterone, impaired blood-testis barrier (BTB), testicular inflammation, and impaired spermatogenesis at tissue/organ levels. Ultimately, decreased sperm quality or quantity was noted and proved by meta-analysis, which demonstrated that MPs/NPs led to a decrease of 5.99 million/mL in sperm concentration, 14.62% in sperm motility, and 23.56% in sperm viability, while causing an increase of 10.65% in sperm abnormality rate. Overall, this is the first AOP for MPs/NPs-mediated male reproductive toxicity in mammals. The innovative integration of meta-analysis into the AOP analysis increases the rigorism of the results.

Exposure to ambient black carbon and particulate matter during pregnancy in associations with risk of pre-eclampsia: A meta-analysis based on population-based studies.

Air pollution control protocols and policies formulated for PM2.5 and PM10 (particulate matter [PM] with an aerodynamic diameter of ≤2.5 and 10 µm), however, such protocols and policies have not been available for black carbon (BC). A growing number of studies have evaluated the association between long-term exposure to ambient air pollution with BC and PM and pre-eclampsia. We applied a meta-analysis to estimate pooled odds ratios (ORs) and 95 % confidence intervals (CIs) based on four exposure windows (first/second/third trimester and entire pregnancy). 24 studies meeting our selection criteria (8 for BC, 21 and 15 for PM2.5 and PM10) were finally included after screening studies published up to June 22, 2023. An increase of 1 µg/m3 BC during the second trimester and entire pregnancy were associated with a 16 % (OR: 1.16, 95 % CI: [1.02, 1.32]) and a 15 % (OR: 1.15, 95 % CI: [1.03, 1.29]) increased risk of pre-eclampsia, respectively. A 10 µg/m3 increase in second-trimester exposure to PM2.5 and PM10 was associated with a 1 % (OR: 1.01, 95 % CI: [1.00, 1.03]) and a 5 % (OR: 1.05, 95 % CI: [1.01, 1.10]) increased risk of pre-eclampsia. An 11 % (OR: 1.11, 95 % CI: [1.03, 1.21]) increased risk of pre-eclampsia was found to be associated with a 10 µg/m3 increase in PM10 exposure during the entire pregnancy. The results support the potential effect of exposure to ambient particulate pollutants on risk of pre-eclampsia and emphasize the necessity of strategies and protocols for controlling BC. Greater efforts in controlling ambient particulate pollution and especially BC are needed in order to prevent pregnant women from developing pre-eclampsia.

Effects of exposure to PM2.5 during pregnancy on the multigenerational reproductive outcomes of male mouse offspring and the role of Sertoli cells.

There is a paucity of studies on the multigenerational reproductive toxicity of fine particle matter (PM2.5) exposure during pregnancy on male offspring and the underlying mechanisms. This study explored the effects of PM2.5 exposure during pregnancy on the spermatogenesis of three consecutive generations of male mouse offspring. We randomized pregnant C57BL/6 mice into the control group, the Quartz Fiber Membrane control group, and two experimental groups exposed to different concentrations of PM2.5 (4.8 and 43.2 mg/kg B.Wt.). Pregnant mice from experimental groups received intratracheal instillation of PM2.5 of different doses on a three-day basis until birth. F1 mature male offspring from PM2.5-exposed pregnant mice were mated with normal female C57BL/6 mice. Likewise, their F2 mature male followed the same to produce the F3 generation. The results showed that PM2.5 exposure during pregnancy led to decreased body and tail length, body weight, and survival rates, decreased sperm concentration and sperm motility, and increased sperm abnormality rates significantly in F1 male offspring. We barely observed significant impacts of PM2.5 on the birth number, survival rates, and index of testes in the F2 and F3 offspring. Further exploration showed that PM2.5 exposure during pregnancy caused the morphological abnormality of Sertoli cells, downregulated androgen receptor (AR) and connexin43, upregulated anti-Müllerian hormone (AMH), cytokeratin-18 (CK-18), caspase-3, and cleaved caspase-3, decreased thyroid-stimulating hormone (TSH) and testosterone (T), and increased triiodothyronine (T3) in F1 male mouse offspring. Overall, we hypothesize that PM2.5 exposure during pregnancy mainly negatively impacts spermatogenesis in the F1 offspring. The possible mechanism could be that PM2.5 exposure during pregnancy disrupts endocrine hormone release in the F1 generation, thereby influencing the maturation and proliferation of their Sertoli cells and hindering spermatogenesis. This study for the first time investigates the role of Sertoli cells in the reproductive toxicity of PM2.5 on offspring.

Prediction models for perineal lacerations during childbirth: A systematic review and critical appraisal.

BACKGROUND: Perineal lacerations could lead to substantial morbidities for women. A reliable prediction model for perineal lacerations has the potential to guide the prevention. Although several prediction models have been developed to estimate the risk of perineal lacerations, especially third- and fourth-degree perineal lacerations, the evidence about the model quality and clinical applicability is scarce. OBJECTIVES: To systematically review and critically appraise the existing prediction models for perineal lacerations. METHODS: Seven databases (PubMed, Embase, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, SinoMed, China National Knowledge Infrastructure, and Wanfang Data) were systematically searched from inception to July 2022. Studies that developed prediction models for perineal lacerations or performed external validation of existing models were considered eligible to include in the systematic review. Two reviewers independently conducted data extraction according to the Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies. The risk of bias and the applicability of the included models were assessed with the Prediction Model Risk of Bias Assessment Tool. A narrative synthesis was performed to summarize the characteristics, risk of bias, and performance of existing models. RESULTS: Of 4345 retrieved studies, 14 studies with 22 prediction models for perineal lacerations were included. The included models mainly aimed to estimate the risk of third- and fourth-degree perineal lacerations. The top five predictors used were operative vaginal birth (72.7 %), parity/previous vaginal birth (63.6 %), race/ethnicity (59.1 %), maternal age (50.0 %), and episiotomy (40.1 %). Internal and external validation was performed in 12 (54.5 %) and seven (31.8 %) models, respectively. 13 studies (92.9 %) assessed model discrimination, with the c-index ranging from 0.636 to 0.830. Seven studies (50.0 %) evaluated the model calibration using the Hosmer-Lemeshow test, Brier score, or calibration curve. The results indicated that most of the models had fairly good calibration. All the included models were at higher risk of bias mainly due to unclear or inappropriate methods for handling missing data and continuous predictors, external validation, and model performance evaluation. Six models (27.3 %) showed low concerns about applicability. CONCLUSIONS: The existing models for perineal lacerations were poorly validated and evaluated, among which only two have the potential for clinical use: one for women undergoing vaginal birth after cesarean delivery, and the other one for all women undergoing vaginal birth. Future studies should focus on robust external validation of existing models and the development of novel models for second-degree perineal laceration. PROSPERO REGISTRATION NUMBER: CRD42022349786. TWEETABLE ABSTRACT: The existing models for perineal lacerations during childbirth need external validation and updating. Tools are needed for second-degree perineal laceration.

MiR-5622-3p inhibits ZCWPW1 to induce apoptosis in silica-exposed mice and spermatocyte cells.

Silica nanoparticles (SiNPs) could cause damage to spermatogenesis, and microRNAs were reported to be associated with male reproduction. This research was designed to explore the toxic impacts of SiNPs induced in male reproduction through miR-5622-3p. In vivo, 60 mice were randomized into the control group and SiNPs group, in which they were exposed to SiNPs for 35 days and then recovered for 15 days. In vitro, 4 groups were set: control group, SiNPs group, SiNPs + miR-5622-3p inhibitor group, and SiNPs + miR-5622-3p inhibitor negative control (NC) group. Our research indicated SiNPs caused the apoptosis of spermatogenic cells, increased level of γ-H2AX, raised the expressions of RAD51, DMC1, 53BP1, and LC8 which were DNA damage repair relative factors, and upregulated Cleaved-Caspase-9 and Cleaved-Caspase-3 levels. Furthermore, SiNPs also elevated the expression of miR-5622-3p but downregulated the level of ZCWPW1. However, miR-5622-3p inhibitor reduced the level of miR-5622-3p, increased the level of ZCWPW1, relieved DNA damage, and depressed the activation of apoptosis pathway, thus, alleviating spermatogenic cells apoptosis caused by SiNPs. The above-mentioned results indicated that SiNPs induced DNA damage resulting in activating of DNA damage response. Meanwhile, SiNPs raised the level of miR-5622-3p targeting inhibited expression of ZCWPW1 to suppress the repair process, possibly making DNA damage so severe that leading to the failure of DNA damage repair, finally inducing the apoptosis of spermatogenic cells.

Radiation-free endoscopic papillectomy for ampullary adenoma: experience from a Chinese tertiary hospital.

BACKGROUND: Conventional endoscopic papillectomy (ESP) for ampullary adenoma is performed as a hybrid endoscopy and fluoroscopy guided procedure. In this study, we report our preliminary experience of non-radiation ESP. METHODS: The present method includes endoscopic snare resection, non-radiation endoscopic biliary and pancreatic stenting and endoclipping. Data from ten patients who underwent non-radiation ESP due to ampullary adenoma were collected. Procedure details, adverse events and follow-up were analyzed. RESULTS: Complete resection was accomplished in all patients, with en bloc resection and piecemeal resection in nine and one patient(s), respectively. Both biliary and pancreatic stenting and biliary stenting alone were achieved in eight and two patients, respectively. Endoclipping was performed in all patients. Hyperleukocytosis and hyperamylasemia occurred in two and one patient(s), respectively. No other complications occurred. No lesion residual or recurrence occurred during follow-up. CONCLUSIONS: Radiation-free ESP can be technically feasible and safely executed by experienced endoscopists. Our study provides a novel strategy for endoscopic resection of major papilla adenoma.

LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma.

Recent researches have uncovered that long non-coding RNAs (lncRNAs) are closely correlated with the development of different diseases, while biological functions and hidden molecular mechanisms of antisense lncRNAs in oesophageal squamous cell carcinoma (OSCC) remain unclear. Here, we identified upregulation of LINC01116 in RNA sequencing data, online database, and in OSCC and intraepithelial neoplasia (IEN) specimens. Functionally, LINC01116 facilitates OSCC advancement and metastasis in vitro and vivo. Mechanistically, elevated expression of LINC01116 in OSCC cells other than tumor stroma and cytoplasmic enables it to activate AGO1 expression via complementary binding with AGO1 mRNA to facilitate EMT process of OSCC.

Silica nanoparticles suppressed the spermatogenesis via downregulation of miR-450b-3p by targeting Layilin in spermatocyte of mouse.

Silica nanoparticles (SiNPs) suppressed spermatogenesis leading to male reproductive toxicity, while the precise mechanism remains uncertain. Here, this study explored the role of miR-450b-3p in male reproductive toxicity induced by SiNPs. In vivo study, we found that SiNPs caused apoptosis of spermatocytes, decreased quantity and quality of sperms, up-regulated the cytoskeleton proteins (Layilin, Talin, and Vinculin), activated the Hippo pathway (Rho A, Yap, and p73), downregulated the expression of miR-450b-3p, damaged the compactness and density of desmosomes between spermatocytes and the basal of the testis. Moreover, in vitro study, we confirmed that SiNPs increased the expressions of cytoskeleton proteins, activated the Hippo pathway, and suppressed miR-450b-3p expressions. Meanwhile, miR-450b-3p mimic inhibited the up-regulation of cytoskeleton proteins, suppressed the activation of the Hippo pathway, and relieved the adhesion and traction stress. Eventually, atomic force microscopy (AFM) was performed to validate the traction stress and adhesion between GC-2spd cells enhanced by deregulation of miR-450b-3p. Taken together, we concluded that SiNPs suppressed spermatogenesis via inhibiting miR-450b-3p, in turn up-regulating the expression of cytoskeleton proteins, then inducing apoptosis via activating the Hippo pathway and enhancing the traction force and adhesion between GC-2spd cells. This work provides novel evidence for the study of reproductive toxicity and risk assessment of SiNPs.

Clinical First-Trimester Prediction Models for Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication that negatively impacts the health of both the mother and child. Early prediction of the risk of GDM may permit prompt and effective interventions. This systematic review and meta-analysis aimed to summarize the study characteristics, methodological quality, and model performance of first-trimester prediction model studies for GDM. METHODS: Five electronic databases, one clinical trial register, and gray literature were searched from the inception date to March 19, 2022. Studies developing or validating a first-trimester prediction model for GDM were included. Two reviewers independently extracted data according to an established checklist and assessed the risk of bias by the Prediction Model Risk of Bias Assessment Tool (PROBAST). We used a random-effects model to perform a quantitative meta-analysis of the predictive power of models that were externally validated at least three times. RESULTS: We identified 43 model development studies, six model development and external validation studies, and five external validation-only studies. Body mass index, maternal age, and fasting plasma glucose were the most commonly included predictors across all models. Multiple estimates of performance measures were available for eight of the models. Summary estimates range from 0.68 to 0.78 (I2 ranged from 0% to 97%). CONCLUSION: Most studies were assessed as having a high overall risk of bias. Only eight prediction models for GDM have been externally validated at least three times. Future research needs to focus on updating and externally validating existing models.

Risk factors for severe perineal lacerations during childbirth: A systematic review and meta-analysis of cohort studies.

AIMS AND OBJECTIVES: To evaluate and quantify the best available evidence regarding risk factors for severe perineal lacerations. BACKGROUND: Many studies have evaluated the risk factors for severe perineal lacerations. However, the results of those studies are inconsistent, and meta-analysis which thoroughly evaluates the risk factors for severe perineal lacerations is still lacking. DESIGN: Systematic review and meta-analysis of cohort studies based on the PRISMA guideline. METHODS: PubMed, Embase, the Cochrane Library, CINAHL, ClinicalTrials.gov, CNKI, Wanfang Data, VIP and SinoMed were systematically searched for cohort studies reporting at least one risk factor for severe perineal lacerations from 1 January 2000 to 2 June 2021. Two reviewers independently conducted quality appraisal by NOS scale and extracted data. Data synthesis was conducted via RevMan 5.3 using a random-effects or fixed-effects model. RESULTS: A total of 47 studies with 7,043,218 women were included. The results showed that prior caesarean delivery (OR: 1.46, 95% CI 1.12-1.92) and pre-pregnant underweight (OR: 1.31, 95% CI 1.22-1.41) significantly increased the risk of severe perineal lacerations. The results also demonstrated that episiotomy was protective against severe perineal lacerations in forceps delivery (OR: 0.56, 95% CI 0.42-0.74), but not spontaneous vaginal delivery (OR: 1.30, 95% CI 0.81-2.07) or vacuum delivery (OR: 0.76, 95% CI 0.45-1.28). Nulliparity, foetus in occipitoposterior or occipitotransverse position, and midline episiotomy were also independent risk factors for severe perineal lacerations. CONCLUSIONS: Severe perineal lacerations are associated with many factors, and evidence-based risk assessment tools are needed to guide the midwives and obstetricians to estimate women's risk of severe perineal lacerations. RELEVANCE TO CLINICAL PRACTICE: This systematic review and meta-analysis identified some important risk factors for severe perineal lacerations, which provides comprehensive insights to guide the midwives to assess women's risk for severe perineal lacerations and take appropriate preventive measures to decrease the risk.

Analyzing toxicological effects of AsIII and AsV to Chlamys farreri by integrating transcriptomic and metabolomic approaches.

Inorganic arsenic (iAs) is a widespread contaminant in marine environments, which is present in two different oxidation states (arsenate (AsV) and arsenite (AsIII)) that have complex toxic effects on marine organisms. The scallop Chlamys farreri (C. farreri) accumulates high levels of As and is a suitable bioindicator of As. In this report, we integrated transcriptomics and metabolomics to investigate genetic and metabolite changes and functional physiological disturbances in C. farreri exposured to inorganic arsenic. Physiological indicators antioxidant factors and cell apoptosis analysis macroscopically corroborated the toxic effects of inorganic arsenic revealed by omics results. Toxic effects of inorganic arsenic on C. farreri were signaling-mediated, causing interference with a variety of cell growth and small molecule metabolism. The results provide evidence that inorganic arsenic disrupts the physiological functions of bivalves, highlighting the correlations between different metabolic pathways and providing new insights into the toxic effects of environmental pollutants on marine organisms.