Prediction of non-dipper blood pressure pattern in Chinese patients with hypertension using a nomogram model.

Non-dipper blood pressure has been shown to affect cardiovascular outcomes and cognitive function in patients with hypertension. Although some studies have explored the influencing factors of non-dipper blood pressure, there is still relatively little research on constructing a prediction model. This study aimed to develop and validate a simple and practical nomogram prediction model and explore relevant elements that could affect the dipper blood pressure relationship in patients with hypertension. A convenient sampling method was used to select 356 inpatients with hypertension who visited the Affiliated Hospital of Jining Medical College from January 2022 to September 2022. All patients were randomly assigned to the training cohort (75%, n = 267) and the validation cohort (25%, n = 89). Univariate and multivariate logistic regression were utilized to identify influencing factors. The nomogram was developed and evaluated based on the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and decision curve analyses. The optimal cutoff values for the prevalence of dipper blood pressure were estimated. The nomogram was established using six variables, including age, sex, hemoglobin (Hb), estimated glomerular filtration rate (eGFR), ejection fraction (EF), and heart rate. The AUC was 0.860 in the training cohort. The cutoff values for optimally predicting the prevalence of dipper blood pressure were 41.50 years, 151.00 g/L, 117.53 mL/min/1.73 m2, 64.50%, and 75 beats per minute for age, Hb, eGFR, ejection fraction, and heart rate, respectively. In summary, our nomogram can be used as a simple, plausible, affordable, and widely implementable tool to predict the blood pressure pattern of Chinese patients with hypertension.

A networked iron and nitrogen-doped ZIF-8/MWCNTs heterostructure for oxygen reduction reaction.

Zeolitic Imidazolate Frameworks-8 (ZIF-8) is commonly used as an ideal precursor for non-noble metal catalysts because of its high specific surface area, ultra-high porosity, and N-rich content. Upon pyrolyzing ZIF-8 at 900 °C in Ar, the resulting material, referred to as Z8, displayed good activity toward the oxygen reduction reaction (ORR). Then the ZIF-8 was mixed with various conductive carbon materials, such as multiwall carbon nanotubes (MWCNTs), Acetylene black (ACET), Vulcan XC-72R (XC-72R), and Ketjenblack EC-600JD (EC-600JD), to form Z8 composites. The Z8/MWCNTs composite exhibited enhanced ORR activity owing to its network structure, meso-/microporous hierarchical porous structure, improved electrical conductivity, and graphitization. Subsequently, iron and nitrogen co-doping is achieved through the pyrolysis of a mixture comprising Fe, N precursor, and ZIF-8/MWCNTs, which is denoted as FeN-Z8/MWCNTs. The intrinsically high electrical conductivity of MWCNTs facilitated efficient electron transfer during the ORR, while the meso-/microporous hierarchical porous structure and network structure of Fe, N co-doped ZIF-8/MWCNTs promoted oxygen transport. The presence of Fe-containing species in the catalyst acted as activity centers for ORR. This strategy of preparing Z8 composites and modifying them with Fe, N co-doping offers an insightful approach to designing cost-effective electrocatalysts.

Health literacy among residents in areas out of poverty in Kunming City / 预防医学

Objective@#To investigate the health literacy and its influencing factors among residents in areas out of poverty in Kunming City, so as to provide insights into formulating health education strategies.@*Methods@#A total of 1 916 permanent residents at ages of 15 to 69 years were sampled in three areas out of poverty in Kunming City using the multi-stage stratified random sampling method and probability proportionate to size sampling method from August to October, 2020. Health literacy was investigated using the Questionnaire on the Health Literacy among Chinese Residents, the level of health literacy was analyzed and weighted by the population of the China's Seventh National Population Census. Factors affecting health literacy among residents in areas out of poverty were identified using a multivariable logistic regression model.@*Results@#A total of 1 916 questionnaires were allocated, and 1 908 valid questionnaires were recovered, with an effective recovery rate of 99.58%. The respondents included 997 men (52.25%) and 911 women (47.75%), and had a mean age of (45.58±14.28) years. The level of health literacy was 21.38%. Multivariable logistic regression analysis identified age (15 to 24 years, OR=5.087, 95%CI: 1.573-16.450; 25 to 34 years, OR=6.016, 95%CI: 1.991-18.183; 35 to 44 years, OR=7.526, 95%CI: 2.541-22.289; 45 to 54 years, OR=4.800, 95%CI: 1.640-14.050), educational level (junior high school, OR=5.333, 95%CI: 3.100-9.175; high school/vocational high school/technical secondary school, OR=19.895, 95%CI: 10.418-37.966; college or above, OR=27.580, 95%CI: 12.349-61.597) as factors affecting health literacy among residents in areas out of poverty in Kunming City.@*Conclusion@#The level of health literacy is 21.38% among residents in areas out of poverty in Kunming City, and age and educational level are associated factors.

Exploring shared pathways and the shared biomarker ERRFI1 in Obstructive sleep apnoea and atherosclerosis using integrated bioinformatics analysis.

Obstructive sleep apnea (OSA) is an upper airway disorder occurring during sleep and is associated with atherosclerosis (AS). AS is a cardiovascular disease caused by environmental and genetic factors, with a high global mortality rate. This study investigated common pathways and potential biomarkers of OSA and AS. Microarray data were downloaded from the Gene Expression Omnibus (GEO) database and used to screen for differentially expressed genes (DEGs) in the OSA and AS datasets. A weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules of OSA and AS. The least absolute shrinkage and selection operators (LASSO) were used to determine critical biomarkers. Immune cell infiltration analysis was used to investigate the correlation between immune cell infiltration and common biomarkers of OSA and AS. Results revealed that differentially expressed genes may be involved in inflammatory processes, chemokine signaling pathways, and molecular changes in cell adhesion. ERBB receptor feedback inhibitor 1 (ERRFI1) was the best-shared biomarker for OSA and AS. Immune infiltration analysis showed that ERRFI1 expression was correlated with immune cell changes. Changes in immune pathways, inflammatory processes, and cell adhesion molecules may underlie the pathogenesis of both diseases, and ERRFI1 may be a potential diagnostic marker for patients with OSA and AS.

A new target of radiotherapy combined with immunotherapy: regulatory T cells.

Radiotherapy is one important treatment for malignant tumours. It is widely believed today that radiotherapy has not only been used as a local tumour treatment method, but also can induce systemic anti-tumour responses by influencing the tumour microenvironment, but its efficacy is limited by the tumour immunosuppression microenvironment. With the advancement of technology, immunotherapy has entered a golden age of rapid development, gradually occupying a place in clinical tumour treatment. Regulatory T cells (Tregs) widely distributing in the tumour microenvironment play an important role in mediating tumour development. This article analyzes immunotherapy, the interaction between Tregs, tumours and radiotherapy. It briefly introduces immunotherapies targeting Tregs, aiming to provide new strategies for radiotherapy combined with Immunotherapy.

Association of dyslipidemia and hypoxemia in patients with obstructive sleep apnea hypopnea syndrome: a cross-sectional study.

OBJECTIVE: Studies have shown that dyslipidemia may contribute to chronic tissue hypoxia. However, it remains unclear whether dyslipidemia affects chronic hypoxia in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Therefore, from a clinical practice perspective, the purpose of this study was to investigate the effect of dyslipidemia on chronic hypoxia in OSAHS patients. METHOD: In athis cross-sectional survey, 320 consecutive OSAHS patients were enrolled. By screening under different conditions, 211 patients were finally enrolled in the study. Patients were grouped according to apnea-hypopnea index (AHI), into a mild-to-moderate (AHI < 30) group and severe OSAHS group (AHI ≥ 30). RESULTS: Comparative analysis shows that 45% of mild-to-moderate OSAHS patients had severe hypoxemia. Univariate and multivariate regression analyses showed that AHI, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) had independent effects on lowest oxygen saturation (LSpO2), and that AHI and TG levels had independent effects on mean oxygen saturation (MSpO2). The patients were stratified by AHI and further grouped by TG and HDL-C abnormalities in each subgroup. A difference analysis showed that LSpO2 and MSpO2 were significantly decreased in OSAHS patients with dyslipidemia (high TG and low HDL-C levels) in the AHI ≥ 30 subgroup (P < 0.05). Finally, in order to further clarify the impact of the selected indicators of hypoxemia in OSAHS patients with different degrees of airway obstruction, subgroup analysis was conducted based on OSAHS severity. In the AHI < 30 subgroup, LSpO2 was significantly decreased in patients with abnormal HDL-C. CONCLUSION: The results of this study indicate that abnormalities in TG and HDL-C, in addition to upper airway obstruction, are among the factors that aggravate chronic hypoxia in tissues from OSAHS patients.

Moving toward a spiritual pedagogy in L2 education: Research, practice, and applications.

Spiritual pedagogy (SP) as a new educational theory aims to apply cultural and spiritual values in classroom practices. It has been the focus of research in different fields such as counselling, management, and science in the past decades. However, its application in second/foreign language research and practice has been widely overlooked by L2 researchers, to date. To fill this gap, the present study made an effort to provide a theoretical analysis of the conceptualizations, scientific background, benefits, and practical techniques to implement SP in the context of L2 education. In so doing, this paper suggests a number of practices through which SP can be integrated into L2 education among which positive psychology (PP) was more highlighted. Additionally, some practical implications were provided for EFL teachers, teacher trainers, students, curriculum designers, and researchers to enhance their knowledge of spirituality and education. In the end, different suggestions for future research were presented to move this research domain forward.

Correlation of serum nicotinamide phosphoribosyl transferase with hypoxia and Framingham risk score in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for atherosclerosis (AS), but the mechanism is different from classical AS risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the pathophysiology of AS via multiple pathways, and its expression is closely related to hypoxia. The association of NAMPT with hypoxia and the risk of cardiovascular morbidity in the patients of OSAHS remains to be defined. Therefore, we carried out this study to investigate the association of NAMPT with hypoxia and the risk of early cardiovascular disease [based on the Framingham risk score (FRS)] in patients with OSAHS. METHODS: A total of 82 patients diagnosed with OSAHS were enrolled in this cross-sectional survey design, along with 18 healthy controls who were age- and gender-matched. The general characteristic parameters including height and weight as well as biochemical parameters including blood glucose and lipid were collected from the subjects. The Framingham vascular risk score calculates the risk of developing vascular disease based on the above indicators. Polysomnography was performed in patients with OSAHS, and blood oxygen saturation and apnea-hypopnea index (AHI) were collected, and patients were grouped by disease extent by AHI. The serum NAMPT level of the research subjects was detected using an enzyme-linked immunosorbent assay. Spearman correlation analysis and multiple linear regression to explore the independent correlations of hypoxia on serum NAMPT activity in OSAHS patients. RESULTS: Serum NAMPT level in patients with OSAHS increased with the severity of the disease. Correlation analysis showed that NAMPT was significantly positively correlated with FRS in patients with OSAHS (r=0.829, P<0.05). Multiple linear regression analysis with FRS as the outcome measure showed that NAMPT activity and minimum blood oxygen saturation were independent associated with the risk of developing cardiovascular disease (ß=0.03, P=0.000; ß=-0.13, P=0.034). Univariate and multivariate regression analyses revealed that hypoxia was significantly associated with NAMPT levels in OSAHS patients, and the oxygen desaturation index (ODI) was independent associated with the expression of NAMPT activity (ß=4.09, P=0.000). CONCLUSIONS: In patients with OSAHS, hypoxia is independently associated with NAMPT. NAMPT increases the risk of cardiovascular morbidity in this population may be influenced by hypoxia.

Metal-Organic Frameworks (MOFs) Derived Materials Used in Zn-Air Battery.

It is necessary to develop new energy technologies because of serious environmental problems. As one of the most promising electrochemical energy conversion and storage devices, the Zn-air battery has attracted extensive research in recent years due to the advantages of abundant resources, low price, high energy density, and high reduction potential. However, the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) of Zn-air battery during discharge and charge have complicated multi-electron transfer processes with slow reaction kinetics. It is important to develop efficient and stable oxygen electrocatalysts. At present, single-function catalysts such as Pt/C, RuO2, and IrO2 are regarded as the benchmark catalysts for ORR and OER, respectively. However, the large-scale application of Zn-air battery is limited by the few sources of the precious metal catalysts, as well as their high costs, and poor long-term stability. Therefore, designing bifunctional electrocatalysts with excellent activity and stability using resource-rich non-noble metals is the key to improving ORR/OER reaction kinetics and promoting the commercial application of the Zn-air battery. Metal-organic framework (MOF) is a kind of porous crystal material composed of metal ions/clusters connected by organic ligands, which has the characteristics of adjustable porosity, highly ordered pore structure, low crystal density, and large specific surface area. MOFs and their derivatives show remarkable performance in promoting oxygen reaction, and are a promising candidate material for oxygen electrocatalysts. Herein, this review summarizes the latest progress in advanced MOF-derived materials such as oxygen electrocatalysts in a Zn-air battery. Firstly, the composition and working principle of the Zn-air battery are introduced. Then, the related reaction mechanism of ORR/OER is briefly described. After that, the latest developments in ORR/OER electrocatalysts for Zn-air batteries are introduced in detail from two aspects: (i) non-precious metal catalysts (NPMC) derived from MOF materials, including single transition metals and bimetallic catalysts with Co, Fe, Mn, Cu, etc.; (ii) metal-free catalysts derived from MOF materials, including heteroatom-doped MOF materials and MOF/graphene oxide (GO) composite materials. At the end of the paper, we also put forward the challenges and prospects of designing bifunctional oxygen electrocatalysts with high activity and stability derived from MOF materials for Zn-air battery.

The efficacy of auto-cross-linked hyaluronic acid gel in addition to oestradiol and intrauterine balloon insertion in the prevention of adhesion reformation after hysteroscopic adhesiolysis.

RESEARCH QUESTION: What is the efficacy of auto-cross-linked hyaluronic acid gel use in preventing adhesion reformation after intrauterine adhesiolysis? DESIGN: This was a single-centre, double-blind randomized controlled trial. RESULTS: In total 171 participants successfully completed the study (84 in the treatment group and 87 in the control group). There was no significant difference in pre-operative variables between the two groups. The primary outcome measure was the adhesion reformation rate at second-look and third-look hysteroscopy. At second-look hysteroscopy, there was no significant difference in adhesion recurrence rate between the treatment group (20.2%, 17/84) and the control group (23.0%, 20/87; P = 0.662). At third-look hysteroscopy, there was also no significant difference in adhesion recurrence rate between the treatment group (9.5%, 8/84) and the control group (11.5%, 10/87; P = 0.675). The secondary outcome measure was the median American Fertility Society (AFS) score, which was not significantly different at second-look hysteroscopy 4 weeks after surgery between the treatment group (0, range 0-4.0) and the control group (0, range 0-4.0; P = 0.475), and at third-look hysteroscopy 8 weeks after surgery between the treatment group (0, range 0-3.5) and the control group (0, range 0-4.0; P = 0.965). Regarding the menstrual flow improvement rate 3 months post-operatively, there was no significant difference between the treatment and control groups (67.9% versus 64.4%; P = 0.630). CONCLUSIONS: The application of auto-cross-linked hyaluronic acid gel does not seem to reduce the incidence and severity of intrauterine adhesion recurrence or affect the menstrual pattern after hysteroscopic removal of mild to moderate intrauterine adhesions.

The Effect of Estrogen in the Prevention of Adhesion Reformation after Hysteroscopic Adhesiolysis: A Prospective Randomized Control Trial.

STUDY OBJECTIVE: To evaluate whether estrogen therapy can reduce adhesion reformation after hysteroscopic adhesiolysis. DESIGN: A single-center, single blinded, randomized controlled trial. SETTING: A tertiary University Hospital. PATIENTS: A total of 207 patients with mild (American Fertility Society [AFS] score 1-6) and severe (AFS score 7-12) intrauterine adhesion who underwent hysteroscopic adhesiolysis. INTERVENTIONS: Patients were randomized to a treatment group or a control group, stratified according to the preoperative AFS adhesion score. The treatment group received estrogen, and the control group did not. All patients had second-look hysteroscopy at 4 weeks and third-look hysteroscopy at 8 weeks after surgery. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were adhesion reformation rate and AFS score at third-look hysteroscopy. Secondary outcome measures included adhesion reformation rate and AFS score at second-look hysteroscopy and menstrual pattern improvement rate at 3 months after operation. Among subjects with mild intrauterine adhesion, there was no significant difference between the treatment group and control group with regard to adhesion reformation rate at third-look hysteroscopy (10.6% vs 13.6%), AFS score (mean ± standard deviation) at third-look hysteroscopy (1.1 ± 1.2 vs 1.3 ± 1.2), and menstrual pattern improvement rate at 3-month follow-up (89.4% vs 86.4%). Similarly, among those with severe intrauterine adhesion, there was no significant difference between the treatment group and control group in adhesion reformation rate at third-look hysteroscopy (32.6% vs 26.7%), AFS score (mean ± standard deviation) at third-look hysteroscopy (2.5±2.2 vs 2.7±2.1), and menstrual pattern improvement rate at 3-month follow-up (84.8% vs 73.3%). CONCLUSION: Postoperative estrogen therapy did not appear to reduce the incidence or severity of adhesion reformation, nor did it improve the menstrual pattern, regardless of whether the pre-existing intrauterine adhesion was mild or severe.

Using thermal forced degradation approach for impurity profiling of budesonide solution-formulated metered dose inhalation with implementation of LC-QTOFMS and HPLC-UV.

The impurity profile of budesonide solution-formulated metered dose inhalation using thermal forced degradation approach was studied intensively in this article. The structural identification of 10 budesonide related impurities was conducted by LC-QTOFMS, and the impurity level in the formulations of different excipients and packing materials were compared using HPLC-UV. Based on our results, the impurities were classified into three groups: (Ⅰ) process impurities, including budesonide impurity A, C and F; (Ⅱ) degradation products, including budesonide impurity E, G, D, 17-carboxylate, and 17-ketone; (Ⅲ) not only process impurities but also degradation products, including budesonide impurity I and L. Budesonide impurity D, 17-carboxylate, 17-ketone and impurity L were found to be the major degradation products of budesonide, and the reaction pathways for the generation of these impurities were speculated. The generation of budesonide impurity D, 17-carboxylate and L was found to be an aerobic oxidation process induced by Al2O3 on the inner surface of aluminum canisters. Furthermore, an in-depth discussion on the proposed impact of the excipients on budesonide degradation, especially on the Al2O3-induced oxidation process, was provided in this article.

Correlation between Body Mass Index and Cognitive Function in Patients with Atrial Fibrillation.

Background: Evidence regarding the relationship between body mass index (BMI) and cognitive function was limited. Therefore, the objective of this research is to investigate whether BMI is independently related to cognitive function in Chinese patients with atrial fibrillation after adjusting for other covariates. Methods: The present study is a cross-sectional study. A total of 281 patients with atrial fibrillation who were hospitalized at the Affiliated Hospital of Jining Medical University in Shandong Province from January 2021 to November 2021 were included in the study. The target independent variable and the dependent variable were BMI and cognitive function in patients with atrial fibrillation, respectively. The patients' general information, BMI, past history, medication history, and other disease-related data were collected. The Montreal cognitive assessment scale (MoCA) was used to evaluate cognitive function. Results: A total of 244 patients with atrial fibrillation were collected in this study, with an average age of (67.28 ± 10.33) years, of whom 55.3% were male. The average BMI was (25.33 ± 4.27) kg/m2, and the average cognitive function score was (19.25 ± 6.88) points. The results of the smooth curve fitting and threshold effect tests showed that there was a curve correlation between BMI and cognitive function score, and its inflection point was 24.56 kg/m2. To the left of the inflection point, the relationship was significant; the effect size and the confidence interval were 0.43 and 0.01-0.85, respectively. To the right of the inflection point, there was no significant correlation between BMI and cognitive function (P=0.152). Conclusion: When BMI is lower than 24.56 kg/m2, the cognitive function score increases by 0.43 points for each unit increase in BMI in patients with atrial fibrillation. An increase in BMI at this time is a protective factor for cognitive function. Within the normal range of BMI, the higher the BMI in atrial fibrillation patients, the higher the cognitive function score. We encourage atrial fibrillation patients with normal BMI to maintain their current weight.

Discovery of STAT3 and Histone Deacetylase (HDAC) Dual-Pathway Inhibitors for the Treatment of Solid Cancer.

Nowadays, simultaneous inhibition of multiple targets through drug combination is an important anticancer strategy owing to the complex mechanism behind tumorigenesis. Recent studies have demonstrated that the inhibition of histone deacetylases (HDACs) will lead to compensated activation of a notorious cancer-related drug target, signal transducer and activator of transcription 3 (STAT3), in breast cancer through a cascade, which probably limits the anti-proliferation effect of HDAC inhibitors in solid tumors. By incorporating the pharmacophore of the HDAC inhibitor SAHA (vorinostat) into the STAT3 inhibitor pterostilbene, a series of potent pterostilbene hydroxamic acid derivatives with dual-target inhibition activity were synthesized. An excellent hydroxamate derivate, compound 14, inhibited STAT3 (KD = 33 nM) and HDAC (IC50 = 23.15 nM) with robust potency in vitro. Compound 14 also showed potent anti-proliferation ability in vivo and in vitro. Our study provides the first STAT3 and HDAC dual-target inhibitor for further exploration.

The association of chronic endometritis with mid-trimester loss due to cervical incompetence and the outcome of laparoscopic cervical cerclage.

PURPOSE: To examine the association of chronic endometritis (CE) with cervical incompetence (CI) in Chinese women with mid-trimester loss, and the impact of the presence of CE on the outcome of laparoscopic cervical cerclage (LCC). METHODS: This retrospective cohort study included a study group of 293 women with mid-trimester loss due to CI (group I) and a comparison group of 332 women with recurrent first-trimester miscarriage (group II). Immunohistochemical study using CD138 epitope for the diagnosis of CE was completed in all subjects. Pre-conception LCC was undertaken in 247 women in the study group (group I). The study was approved by Institutional Review Board (IRB) (number 2015FXHEC-KY005). RESULTS: The prevalence of CE in group I was 42%, significantly (P < 0.001) higher than that of 23.5% in group II. Among 247 women in group I, there were no significant difference in mid-trimester loss rate, preterm delivery rate and term delivery rate in women with and without CE (2.2, 12.0, 85.8% vs. 1.8, 10.1, 88.1% respectively) and between women with CE treated and not treated with antibiotics prior to conception (2.3, 9.3, 88.4% vs. 2.0, 14.3, 83.7% respectively). CONCLUSIONS: Mid-trimester loss due to cervical incompetence is associated with chronic endometritis; However, the presence or not of CE and whether it was treated with antibiotics prior to conception did not appear to significantly influence the obstetric outcomes of women with CI after LCC.

Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial.

OBJECTIVE: To compare the rates of negative test results for chronic endometritis (CE) between subjects who did and did not receive antibiotic treatment. DESIGN: Prospective, single-blind randomized controlled trial. SETTING: Tertiary hysteroscopic center in a university teaching hospital. PATIENT(S): A total of 132 women with CE confirmed with immunohistochemical study with CD138 epitope. INTERVENTION(S): Women randomized to antibiotic therapy received oral levofloxacin 500 mg and tinidazole 1,000 mg daily for 14 days. Women randomized to the control group did not receive any treatment. A repeated endometrial biopsy was performed 4 to 8 weeks after the initial biopsy to determine whether CE was still present. MAIN OUTCOME MEASURE(S): The rate of negative test results for CE (from positive to negative). RESULT(S): The CE rate of negative test results in the treatment group (89.3%) after one course of antibiotic treatment was significantly higher than that in the control group (12.7%). Among subjects who attempted pregnancy, there was no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (43.2%, 5.4%) and the control arm (25.7%, 14.3%). Among subjects randomized, there was also no significant difference in ongoing pregnancy rates and miscarriage rates between the treatment arm (27.1%, 3.4%) and the control arm (16.4%, 9.1%). CONCLUSION: A course of broad-spectrum oral antibiotic therapy for 14 days is effective in the treatment of CE in >89.8% of cases. However, it is not yet clear whether treatment improved pregnancy outcomes. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT02648698.

CircPlekha7 plays an anti-fibrotic role in intrauterine adhesions by modulating endometrial stromal cell proliferation and apoptosis.

Circular RNA (circRNA) plays a key role in the development and progression of several diseases; however, its role in intrauterine adhesions (IUAs) is not well understood. This study aims to investigate the expression profiles and potential role of circRNA in IUA. RNA-sequencing was performed to screen for abnormally expressed circRNAs in TGF-ß1-induced IUA endometrial stromal cell (ESC) model (IUA group) and an SMAD3 inhibitor, SIS3-treated IUA ESC model (SIS3 group). Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to uncover the key functions and pathways. Interaction networks were constructed and analyzed based on the competing endogenous RNA hypothesis of circRNA. CircRNAs were validated by Sanger sequencing and quantitative polymerase chain reaction (qPCR). Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. The protein and mRNA expression levels of fibrosis-related proteins were measured using western blotting and reverse transcription-qPCR, respectively. A total of 66 circRNAs were differentially expressed between the IUA and SIS3 groups. CircPlekha7 was identified as one of the significantly upregulated circRNAs in the SIS3 group. Overexpression of circPlekha7 enhanced apoptosis, decreased the viability of ESCs, and suppressed the expression of α-SMA, collagen I, and SMAD3 in ESCs; whereas knockdown of circPlekha7 exhibited opposite results. Altogether, the results indicate that circPlekha7 plays an anti-fibrotic role in IUA and may serve as a promising prognostic biomarker for patients with IUA. Therefore, overexpression of circPlekha7 could be a potential treatment strategy for IUA.

Functional analysis of miRNAs combined with TGF-ß1/Smad3 inhibitor in an intrauterine rat adhesion cell model.

In this study, we aimed to study the role of miRNAs in intrauterine adhesion (IUA) disease. An IUA cell model was constructed by TGF-ß1. Smad3 inhibitor (SIS3) can inhibit the Smad3 signaling pathway and affect the role of TGF-ß1; thus, it was used to identify the role of Smad3 and related miRNAs in IUA. Cell number significantly increased in the TGF-ß1 group after 72 h and 96 h, respectively, compared with that in the control group (P < 0.05). However, cell proliferation was significantly decreased in the TGF-ß1 + SIS3 group (P < 0.0001). Cell apoptosis was increased in the TGF-ß1 + SIS3 group compared with that in the TGF-ß1 group. Western Blot (WB) analysis suggested that TGF-ß1 treatment could effectively increase the expression of α-SMA, COL1, Smad3, and p-Smad3, which could be inhibited by SIS3 treatment. A total of 235 and 530 differentially expressed miRNAs in the TGF-ß1 + SIS3 group were significantly up- and downregulated compared with those in the TGF-ß1 group, respectively. These differentially expressed miRNAs were enriched in the MAPK and PI3K-AKT pathways. The ten most differentially expressed miRNAs were selected to verify their expressions using quantitative real-time polymerase chain reaction (qPCR). Furthermore, overexpression of rno-miR-3586-3p and rno-miR-455-5p can promote cell proliferation and exacerbate the IUA pathogenic process. However, overexpression of rno-miR-204-3p and rno-miR-3578 can inhibit cell behavior and IUA progression. The above results can provide detailed information for the understanding of IUA molecular mechanisms.