Electrophysiologic mechanism and ablation strategy for macroreentrant biatrial tachycardias after Cox-maze procedures.

BACKGROUND: Different types of recurrent atrial tachycardia (AT) after Cox-maze procedures have been reported, whereas biatrial tachycardia (BiAT) has not been systematically analyzed. OBJECTIVE: In this study, we retrospectively investigated the electrophysiologic characteristics of BiAT after Cox-maze procedures by use of an ultrahigh-density mapping system. METHODS: Of a consecutive 76 patients who underwent catheter ablation of AT after Cox-maze procedures, 12 BiATs were identified. High-density activation mapping was performed in both the left atrium and right atrium in combination with entrainment pacing to confirm the circuit. RESULTS: We classified these BiATs into 2 groups. In group 1 (7 patients), the bidirectional block of maze linear lesions to prevent the macroreentrant AT was achieved; the posterior interatrial connections were involved in the circuit. In group 2 (5 patients), the bidirectional block of maze linear lesions was not blocked, and the most common gap was located at the end of the linear lesion near the annulus. In group 1, all the ATs were terminated by targeting the corresponding left atrium end of the posterior interatrial connections. In group 2, the ATs were terminated by targeting the gap near the annulus. CONCLUSION: The optimal ablation strategy for BiATs after the maze procedure should be based on detailed demonstration of the circuit by high-density mapping.

On the relative conservativeness of Bayesian logistic regression method in oncology dose-finding studies.

The Bayesian logistic regression method (BLRM) is a widely adopted and flexible design for finding the maximum tolerated dose in oncology phase I studies. However, the BLRM design has been criticized in the literature for being overly conservative due to the use of the overdose control rule. Recently, a discussion paper titled "Improving the performance of Bayesian logistic regression model with overall control in oncology dose-finding studies" in Statistics in Medicine has proposed an overall control rule to address the "excessive conservativeness" of the standard BLRM design. In this short communication, we discuss the relative conservativeness of the standard BLRM design and also suggest a dose-switching rule to further enhance its performance.

Efficacy and safety of the vein of Marshall ethanol infusion with radiofrequency catheter ablation for the treatment of persistent atrial fibrillation in elderly patients.

Background: Increasing age is a significant risk factor for atrial fibrillation (AF) recurrence after catheter ablation (CA). We accomplished this study to evaluate the efficacy and safety of the vein of Marshall (VOM) ethanol infusion (VOM-EI) with CA in elderly patients with persistent AF (PsAF). Methods: This retrospective observational study included 360 consecutive adult patients with PsAF, of which 141 were in the Elder group (age ≥65 years) and 219 were in the Younger group (age <65 years), who underwent the VOM-EI and radiofrequency CA (RFCA) between May 2020 and April 2022. The efficacy endpoint was no recurrence of AF within one year after CA. Results: The VOM-EI was successfully performed in 90.8% of patients from the Elder and 88.6% from the Younger group. All patients achieved PVI; 97.9% of patients from the Elder and 98.6% from the Younger group reached LA roof block, and 93.6% of patients from the Elder and 95.9% from the Younger group achieved MI block. There was no significant difference in 1-year survival without recurrence of AF between the two groups (83.0% and 84.5%, respectively). The incidence of complications within 30 days after the procedure from the two groups was low and did not differ significantly. Conclusion: The VOM-EI combined with RFCA proved to be an effective and safe strategy for treating PsAF in elderly and younger patients.

Exploration and analysis of a generalized one-parameter item response model with flexible link functions.

This paper primarily analyzes the one-parameter generalized logistic (1PGlogit) model, which is a generalized model containing other one-parameter item response theory (IRT) models. The essence of the 1PGlogit model is the introduction of a generalized link function that includes the probit, logit, and complementary log-log functions. By transforming different parameters, the 1PGlogit model can flexibly adjust the speed at which the item characteristic curve (ICC) approaches the upper and lower asymptote, breaking the previous constraints in one-parameter IRT models where the ICC curves were either all symmetric or all asymmetric. This allows for a more flexible way to fit data and achieve better fitting performance. We present three simulation studies, specifically designed to validate the accuracy of parameter estimation for a variety of one-parameter IRT models using the Stan program, illustrate the advantages of the 1PGlogit model over other one-parameter IRT models from a model fitting perspective, and demonstrate the effective fit of the 1PGlogit model with the three-parameter logistic (3PL) and four-parameter logistic (4PL) models. Finally, we demonstrate the good fitting performance of the 1PGlogit model through an analysis of real data.

Mechanical characteristics analysis and control algorithm for floating raft system with mass variation.

The ship floating raft system adopts the integrated design of large liquid tanks and rafts, which can optimize the arrangement in the cabin and increase the intermediate mass of the system to achieve efficient vibration isolation of equipment. One of the major challenges is that the change of liquid mass in the tank will cause displacement of the raft, which will change the modal characteristics of the system and affect the stability of the vibration isolation system performance. This paper establishes a mechanical analysis model of a floating raft system under time-varying liquid mass conditions. Taking a ship variable mass floating raft system as the research object, the effect of mass change on the characteristics of raft displacement, isolator load distribution, and modal frequency of the vibration isolation system is analyzed. The analysis shows that when the liquid tank goes from full load to no-load state, its mass change accounts for 40% of the total mass of the raft, which will cause a large displacement of the raft and change the low order modal frequency of the system, bringing the risk of equipment safety and vibration isolation performance degradation. Therefore, an adaptive variable load control method is proposed to realize the raft attitude balance and load equalization optimization under the variable mass condition of the floating raft air spring system. The test results show that the proposed control method can automatically adapt to the large mass gradual change from full load to no load of the liquid tank on the raft, and control the displacement of the raft structure from about 10 mm to 1.5 mm, which effectively ensures the stability of the air spring system performance.

Application of three-dimensional multi-imaging combination in brachytherapy of cervical cancer.

BACKGROUND: Three-dimensional (3D) imaging has an important role in brachytherapy and the treatment of cervical cancer. The main imaging methods used in the cervical cancer brachytherapy include magnetic resonance imaging (MRI), computer tomography (CT), ultrasound (US), and positron emission tomography (PET). However, single-imaging methods have certain limitations compared to multi-imaging. The application of multi-imaging can make up for the shortcomings and provide a more suitable imaging selection for brachytherapy. PURPOSE: This review details the situation and scope of existing multi-imaging combination methods in cervical cancer brachytherapy and provides a reference for medical institutions. MATERIALS AND METHODS: Searched the literature related to application of three-dimensional multi-imaging combination in brachytherapy of cervical cancer in PubMed/Medline and Web of Science electronic databases. Summarized the existing combined imaging methods and the application of each method in cervical cancer brachytherapy. CONCLUSION: The current imaging combination methods mainly include MRI/CT, US/CT, MRI/US, and MRI/PET. The combination of two imaging tools can be used for applicator implantation guidance, applicator reconstruction, target and organs at risk (OAR) contouring, dose optimization, prognosis evaluation, etc., which provides a more suitable imaging choice for brachytherapy.

Circulating lncRNAs NONHSAT054669.2 and ENST00000525337 can be used as early biomarkers of gestational diabetes mellitus.

Early diagnosis can help prevent and reduce the adverse effects of gestational diabetes mellitus (GDM). This study intended to investigate key circulating long non-coding RNAs (lncRNAs) as novel biomarkers for diagnosis of GDM at the early stages. First, lncRNA microarray analysis was conducted for plasma samples of GDM women before delivery and 48 h after delivery. The expression of differentially expressed lncRNAs in clinical samples at different trimesters was randomly validated by quantitative polymerase chain reaction (PCR). Moreover, the correlation between lncRNA expression and oral glucose tolerance test (OGTT) level in GDM women during the second trimester was analyzed, followed by evaluating the diagnostic value of key lncRNAs during different trimesters using receiver operating characteristic (ROC) curve. Higher NONHSAT054669.2 expression and lower ENST00000525337 expression were revealed in GDM women before delivery relative to 48 h after delivery (P < 0.05). The expression of NONHSAT054669.2 and ENST00000525337 in GDM women during the first and second trimesters was dramatically higher than pregnant women (P < 0.05) with normal glucose tolerance (NGT). During the second trimester, NONHSAT054669.2 expression was positively related to OGTT level at 1 h (r = 0.41455, P < 0.001). Furthermore, ROC curve analysis revealed that ENST00000525337 alone, NONHSAT054669.2 alone, and their combination had high diagnostic value for GDM during the first (area under the ROC curve (AUC) = 0.979, 0.956, and 0.984, respectively) and second (AUC = 0.829, 0.809, and 0.838, respectively) trimesters (all P < 0.001). The plasma level of NONHSAT054669.2 and ENST00000525337 may be applied as novel diagnostic biomarkers for early diagnosis of GDM.

The MRI-guided two adaptive brachytherapy fractions versus one adaptive brachytherapy fraction in one application for the cervical cancer: a retrospective study.

PURPOSE: This study retrospectively compared the clinical and toxicity outcomes for the cervical cancer of the MRI-guided two adaptive brachytherapy (IGABT) fractions versus one IGABT fraction in one application. METHODS: One hundred and twenty patients with cervical cancer received external beam radiotherapy combined with or without concurrent chemotherapy, which was followed by the IGABT. The IGABT in 63 patients had one IGABT in each application (Arm 1), while in the other 57 patients, at least one treatment was two continuous IGABT every other day in one application (Arm 2). Clinical outcomes including overall survival (OS), cancer specific survival (CSS), progression free survival (PFS), local control (LC) were analyzed. Brachytherapy-related toxicities were evaluated, which included pain, dizziness, nausea/vomiting, fever/infection, blood loss during the removal of applicator and needles, the deep venous thrombosis, and other acute toxicities. The Common Terminology Criteria for Adverse Events (CTC-AE 5.0) was used to evaluate the incidence and severity of toxicities of the urinary system, lower digestive system, and reproduction system. Kaplan-Meier and the Log-rank test were used to analyze the clinical outcomes. RESULTS: The median follow-up time of the patients in Arm 1 and Arm 2 was 23.5 and 12.0 months, respectively. The overall treatment time was significantly shorter in Arm 2 than Arm 1 (60 vs. 64 d; P = 0.017). The OS, CSS, PFS, and LC in Arm1 and Arm 2 was 77.8% vs. 86.0% (P = 0.632), 77.8% vs. 87.7% (P = 0.821), 68.3% vs. 70.2% (P = 0.207), and 92.1% vs. 94.7% (P = 0.583), respectively. The highest NRS of the pain during brachytherapy waiting period (2.22 ± 1.84 vs. 3.02 ± 1.65; P < 0.001) and at the time of the removal of the applicator (4.69 ± 1.49 vs. 5.30 ± 1.18; P < 0.001) in the patients who received one hybrid intracavitary and interstitial brachytherapy (IC/ISBT) in one application and two continuous IC/ISBT every other day in one application were significantly different. So far four patients with grade 3 late toxicities have been reported. CONCLUSIONS: The findings of this study demonstrated that the two continuous IGABT every other day in one application is a logistically applicable, safe, and effective treatment strategy that could shorten the overall treatment time and reduce the medical cost, comparing with the one IGABT in one application.

Dose-effect relationship between dose-volume parameters of residual gross tumor volume and clinical prognosis in MRI-guided adaptive brachytherapy for locally advanced cervical cancer: a single-center retrospective study.

PURPOSE: To investigate the dose-effect relationship between the dose-volume parameters of residual gross tumor volume (GTVres) and clinical prognosis in MRI image-guided adaptive brachytherapy (IGABT) of patients with locally advanced cervical cancer in our center. MATERIALS AND METHOD: The clinical data of 93 patients with locally advanced cervical squamous cell cancer who received external beam radiotherapy (EBRT) combined with IGABT ± chemotherapy in our center were retrospectively analyzed. The disease stage, overall treatment time (OTT), chemotherapy, and the dose-volume parameters D90, D98, and D100 of GTVres, the intermediate-risk clinical target volume (CTVIR), and the high-risk clinical target volume (CTVHR) of the patients were statistically analyzed. Kaplan-Meier and uni- and multivariable Cox regression analyses were used to analyze 2­year overall survival (OS), progression-free survival (PFS), and local control rate (LC). A probit model was employed to assess the dose-effect relationship between the volume and dose-volume parameters of GTVres and 2­year OS, PFS, and LC. RESULTS: The median follow-up time was 19.6 months and 2­year OS, PFS, and LC were 79.6%, 68.8%, and 94.6%, respectively. CTVHR D90 was an independent influencing factor for 2­year PFS (P = 0.041); GTVresBT1 volume was an independent factor for 2­year OS, PFS, and LC (P < 0.001). The probit model showed that at GTVresBT1 volume < 32.86 cm3, the expected 2­year LC was > 90%; at GTVres D98 > 129.12 GyEQD2, the expected 2­year OS was > 90%. CONCLUSION: Both the volume and dose-volume parameters of GTVres are promising predictors in assessment of IGABT prognosis of cervical cancer.

Emergence of electric-field-tunable interfacial ferromagnetism in 2D antiferromagnet heterostructures.

Van der Waals (vdW) magnet heterostructures have emerged as new platforms to explore exotic magnetic orders and quantum phenomena. Here, we study heterostructures of layered antiferromagnets, CrI3 and CrCl3, with perpendicular and in-plane magnetic anisotropy, respectively. Using magneto-optical Kerr effect microscopy, we demonstrate out-of-plane magnetic order in the CrCl3 layer proximal to CrI3, with ferromagnetic interfacial coupling between the two. Such an interlayer exchange field leads to higher critical temperature than that of either CrI3 or CrCl3 alone. We further demonstrate significant electric-field control of the coercivity, attributed to the naturally broken structural inversion symmetry of the heterostructure allowing unprecedented direct coupling between electric field and interfacial magnetism. These findings illustrate the opportunity to explore exotic magnetic phases and engineer spintronic devices in vdW heterostructures.

Hexagonal Network of Photocurrent Enhancement in Few-Layer Graphene/InGaN Quantum Dot Junctions.

Strain in two-dimensional (2D) materials has attracted particular attention because of the remarkable modification of electronic and optical properties. However, emergent electromechanical phenomena and hidden mechanisms, such as strain-superlattice-induced topological states or flexoelectricity under strain gradient, remain under debate. Here, using scanning photocurrent microscopy, we observe significant photocurrent enhancement in hybrid vertical junction devices made of strained few-layer graphene and InGaN quantum dots. Optoelectronic response and photoluminescence measurements demonstrate a possible mechanism closely tied to the flexoelectric effect in few-layer graphene, where the strain can induce a lateral built-in electric field and assist the separation of electron-hole pairs. Photocurrent mapping reveals an unprecedentedly ordered hexagonal network, suggesting the potential to create a superlattice by strain engineering. Our work provides insights into optoelectronic phenomena in the presence of strain and paves the way for practical applications associated with strained 2D materials.

A prospective study of radical external beam radiotherapy versus external beam radiotherapy combined with intraluminal brachytherapy for primary esophageal cancer.

PURPOSE: This study compared the efficacy and side effects of external beam radiotherapy (EBRT) + intraluminal brachytherapy (IBT) with EBRT alone in patients with primary thoracic esophageal cancer. MATERIALS AND METHODS: Between 2013 and 2020, 64 patients with primary thoracic esophageal cancer without surgery received radiotherapy. Thirty-two patients received EBRT + IBT. EBRT dose was 50 Gy, 2 Gy/f, 5 times a week, and IBT dose was 10 Gy, 5 Gy/f, once a week. Thirty-two patients received EBRT alone, and the total dose was 60 Gy. The median followup was 19 months. RESULTS: The local control rates (LCR) of EBRT + IBT and EBRT alone group at 1, 2, and 3 years after treatment were 88% and 72%, 53% and 22%, 25%, and 9%, respectively. The overall survival (OS) of the EBRT + IBT and EBRT alone group at 3 years after treatment were 38% and 9%. The 3-year local recurrence-free survival (LRFS) rates of EBRT + IBT and EBRT alone group were 25% and 9%. Univariate analysis showed that EBRT + IBT could be the prognostic factor improving OS (p = 0.04), and tumor located in the mid-thoracic region exhibited a poorer prognosis on LRFS (p = 0.03). Grade 3 or higher acute side effects included two cases of dysphagia and three cases of bone marrow suppression. Severe late side effects included three cases of fistula, three cases of radiation pneumonia, and five cases of stenosis requiring treatment. CONCLUSIONS: Compared with EBRT alone, EBRT + IBT is an effective treatment modality for T1∼3NanyM0 primary thoracic esophageal cancer with good local control. It can prolong the survival time of patients and has acceptable toxicity.

Quantitative analysis of contrast-enhanced ultrasound combined with ultrasound in the unifocal papillary thyroid micro-carcinoma.

OBJECTIVE: To evaluate diagnostic value of ultrasound (US) combined with contrast-enhanced ultrasound (CEUS) in the invasiveness of unifocal papillary thyroid micro-carcinoma (UPTMC) without capsule-invasion. METHODS: This retrospective study included data from patients with UPTMC who received US and CEUS examinations in the Ultrasound Department of the Central Hospital of Changsha, China between June 2019 and September 2021. Univariate and multivariate logistic regression analysis were used to evaluate the risk of US and CEUS parameters for UPTMC. Diagnostic performance was estimated by ROC analysis. RESULTS: A total of 136 cases were enrolled, including invasive UPTMC (n = 47) and non-invasive UPTMC (n = 89), which were divided into test set (n = 109) and validation set (n = 27). The occurrence of microcalcification and the ratios (R) of each time-intensity curve (TIC) of CEUS parameter were significantly higher in patients with invasive UTPMC than non-invasive UPTMC (all P < 0.05). Additionally, nodular diameter was significantly longer in the invasive group (P < 0.05). Multivariate analysis showed that microcalcification (OR = 2.917, 95% CI: 1.002-8.491, P = 0.050), R-TTP > 1 (OR = 3.376, 95%CI: 1.267-8.994, P = 0.015), R-DS > 1 (OR = 6.558, 95% CI: 2.358-18.243, P < 0.010) were independently associated with invasive UPTMC. The sensitivities of US, CEUS and their combined application were 82.1%, 46.2% and 79.5%, respectively, and their specificities were 37.1%, 88.6% and 61.4%, respectively. The combination of the two methods had the best diagnostic efficiency (AUC=0.775)compared to US (AUC = 0.596) and CEUS (AUC = 0.750). CONCLUSION: The combination of US and CEUS might have good diagnostic value for UPTMC with capsule non-invasion.

Clinical Outcomes of MRI-Guided Adaptive Brachytherapy for Each Fraction in Locally Advanced Cervical Cancer: A Single Institution Experience.

Purpose: This study aims to evaluate clinical outcomes of MRI-guided adaptive brachytherapy (MR-IGABT) for each brachytherapy fraction in patients with locally advanced cervical cancer (LACC). Methods and Materials: A retrospective analysis was performed on 97 consecutive patients with LACC treated with 44.0-50.4 Gy external beam radiotherapy (EBRT) ± concurrent platinum-containing chemotherapy followed by 4 × 7 Gy MR-IGABT between September 2014 and April 2019. Intracavitary (IC)/interstitial (IS)/hybrid intracavitary and interstitial (IC/IS) brachytherapy was used in MR-IGABT. Brachytherapy planning and dose reporting followed the GEC-ESTRO recommendations. Clinical outcomes including overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), local control (LC), and treatment-related toxicity evaluated by the RTOG criteria were analyzed. Kaplan-Meier and univariable and multivariable Cox regression analyses were used to analyze the prognostic factor. Results: Median follow-up was 21.1 months. Median dose to 90% (D90) of the high-risk clinical target volume (HR-CTV) was 91.7 Gy (range 76.7~107.2 Gy). Two-year OS, CSS, PFS, and LC were 83.5%, 84.1%, 71.1%, and 94.8%, respectively. Four patients (4.1%) suffered from grade 3 late gastrointestinal radiation toxicity, and no other grade 3 or greater radiation toxicity occurred. Initial HR-CTV was an independent factor of OS (p = 0.001, HR = 1.018/cm3), PFS (p = 0.012, HR = 1.012/cm3), and LC (p = 0.011, HR = 1.028/cm3). The HR-CTV D90 (p = 0.044, HR = 0.923/Gy) was an independent factor of PFS. Age was an independent factor of LC (p = 0.010, HR = 1.111/year). Conclusion: For patients with LACC, MR-IGABT was effective and safe. It showed favorable LC, OS, and minimal toxicity. Moreover, initial HR-CTV, HR-CTV D90, and age were significant prognostic factors.

Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR).

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

RNA-seq analysis of peripheral blood dendritic cells maturated by dezocine in patients with lung cancer.

Surgical resection is the most common and effective option for the clinical treatment of lung cancer. Postoperative pain may activate surgically induced stress response, leading to a decrease in human immune function. However, conventional analgesics such as morphine and its derivatives have been reported to have immunosuppressive side effects. In the critical period after surgery, the immunosuppressive effect of analgesics on patients with lung cancer could promote postoperative cancer recurrence and metastasis. Therefore, it will be an ideal scenario for postoperative pain management to maximize pain relief while minimizing immunosuppression side effects. In this study, we found that a novel mixed agonist-antagonist opioid analgesic, dezocine, significantly promoted the morphological maturation of dendritic cells (DCs), and increase the expression of DCs-related surface markers in postoperative peripheral blood of patients with lung cancer. Furthermore, dezocine-matured DCs increased the general immune response by promoting the secretion of IL-12 and IL-6 cytokines and enhancing the proliferation and cytotoxicity of CD8+ T cells. Then genome-wide transcriptomic profiling analyses were performed to identify the specific gene expression of dezocine-matured DCs. The results of transcriptomic analysis as well as in vitro validation showed that the upregulation of CXCL10, CD3G, and GRB2 were significantly associated with dezocine-induced DCs maturation. Overall, our data showed that dezocine might exhibit unique properties by acting as an immunostimulant, which provides new evidence for its application in postoperative pain management of patients with lung cancer.

Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM.

BACKGROUND: Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM. METHODS: We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages. RESULTS: Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001). CONCLUSION: Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

The association of telomere maintenance and TERT expression with susceptibility to human papillomavirus infection in cervical epithelium.

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervical intraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.

[Intervention effects of estradiol on myocardial ischemia- reperfusion injury of rat and its mechanisms].

Objective: To study the effects of estradiol (E2) on alleviating myocardial ischemia/reperfusion(I/R) injury through estrogen receptorß(ERß) mediated extracellular regulated protein kinases(ERK) pathway activation. Methods: Eighty-four adult female SD rats were ovariectomized and randomly divided into control group, NC siRNA adeno-associated virus (AAV) group received sham operation, the myocardial I/R injury model was prepared by ligation of the left anterior descending coronary artery in I/R group, E2+I/R group, NC siRNA AAV+I/R group, NC siRNA AAV+E2+I/R group and ERß-siRNA AAV+E2+I/R group. E2+I/R group, NC siRNA AAV+E2+I/R group and ERß-siRNA AAV+E2+I/R group were treated with E2 0.8 mg/kg by gavage for 60 days before modeling. NC siRNA AAV+I/R group, NC siRNA AAV+E2+I/R group, and ERß-siRNA AAV+E2+I/R group were treated with AAV by caudal vein injection 24 h before modeling. After 120 min of reperfusion, the contents of serum lactate dehydrogenase (LDH), phosphocreatine kinase (CK), phosphocreatine kinase isoenzyme (CK-MB), myocardial infarction area and the expressions of ERß, p-ERK, the contents of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1 ß), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in myocardium were measured. Results: The contents of serum LDH, CK, CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 ß, MDA in myocardium of I/R group were higher than those of the control group, the expression levels of ERß and p-ERK and the content of T-AOC were lower than those in the control group (P＜0.05). The contents of serum LDH, CK and CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 ß and MDA in myocardium of E2+I/R group were lower than those of the I/R group, the expression levels of ERß and p-ERK and the content of T-AOC were higher than those of the I/R group(P＜0.05). After knockdown ERß by caudal vein injection of ERß-siRNA AAV, the contents of serum LDH, CK and CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 ß and MDA in myocardium of ERß-siRNA AAV+E2+I/R group were higher than those of NC-siRNA AAV+E2+I/R, the expression levels of ERß and p-ERK and the content of T-AOC were lower than those of NC-siRNA AAV+E2+I/R(P＜0.05). Conclusion: E2 has protective effects on myocardial I / R injury in ovariectomized rats, which are related to the promotion of ERß mediating the activation of ERK pathway, reducing inflammatory and oxidative stress responses.