Effects of STAT4 on myocardial ischemia­reperfusion injury and the underlying mechanisms.

The regulation of cardiac function by the nuclear transcription factor signal transducer and activator of transcription 4 (STAT4) has been recently recognized. Nevertheless, the role and mechanisms of action of STAT4 in myocardial ischemia­reperfusion (I/R) injury remain unknown. Consequently, the present study constructed a rat model of I/R by ligation of the left anterior descending coronary artery. Following sacrifice, the rat hearts were excised and analyzed to investigated the effects of STAT4 on I/R­induced myocardial injury. Western blotting demonstrated that expression of STAT4 decreased significantly in the rat model of cardiac I/R and in H9C2 cells that were subjected to hypoxia and reoxygenation (H/R). The overexpression of STAT4 in H9C2 cells reduced cell damage and apoptosis induced by H/R. Furthermore, both in vivo and in vitro, the level of PI3K decreased significantly. Although the AKT protein expression levels were not altered, the AKT phosphorylation levels decreased significantly. STAT4 overexpression enhanced the expression of PI3K and AKT in the H9C2 cells. On the whole, the present study demonstrated that STAT4 alleviated I/R­induced myocardial injury through the PI3K/AKT signaling pathway.

Intrapericardial Administration of Human Pericardial Fluid Cells Improves Cardiac Functions in Rats with Heart Failure.

Heart failure (HF) is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced HF rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (N = 5). These cells that primarily expressed SCA-1, NANOG, and mesenchymal markers, CD90, CD105, and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 × 105 cells/heart) were injected into the pericardial cavity of the DOX-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted red fluorescent protein-tagged hPFCs coexpressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFC treatment (P < 0.0001 vs. untreated). The elevated inflammatory cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α in the DOX-treated hearts were found to be significantly reduced (P < 0.001 vs. untreated), while the regional proangiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFC-treated group after 4 weeks (P < 0.05 vs. untreated). hPFCs possess stem cell characteristics and can improve the cardiac functions of DOX-induced HF rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional proangiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.

Pirfenidone improves early cardiac function following myocardial infarction by enhancing the elastin/collagen ratio.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio. METHODS: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression. RESULTS: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1ß (IL-1ß), IL-6, and transforming growth factor-ß (TGF-ß). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1ß, IL-6, TGF-ß, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio. CONCLUSION: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.

Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage.

Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration. Here, single-cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity. After stringent quality control, high-quality data were obtained from 32,014 cells. Distinct cell clusters comprising stromal and immune cells were identified in ligament tissues. Among them, we noted that collagen degradation associated with CTHRC1+ fibroblast-like cells and calcification linked to CRTAC1+ chondrocyte-like cells were key features of ligament degeneration. SCENIC analysis and further experiments identified ATF3 as a key transcription factor regulating the pathogenesis of CRTAC1+ chondrocyte-like cells. Typically, immune cells infiltrate localized organs, causing tissue damage. In our study, myeloid cells were found to be inflammatory-activated, and SPP1+ macrophages were notably enriched in degenerative ligaments. Further exploration via CellChat analysis demonstrated a robust interaction between SPP1+ macrophages and CRTAC1+ chondrocyte-like cells. Activated by SPP1, ATF3 propels the CRTAC1/MGP/CLU axis, fostering ligament calcification. Our unique resource provides novel insights into possible mechanisms underlying ligament degeneration, the target cell types, and molecules that are expected to mitigate degenerative spinal ligament. We also highlight the role of immune regulation in ligament degeneration and calcification, enhancing our understanding of this disease.

Wavelet-based U-shape network for bioabsorbable vascular stents segmentation in IVOCT images.

Background and Objective: Coronary artery disease remains a leading cause of mortality among individuals with cardiovascular conditions. The therapeutic use of bioresorbable vascular scaffolds (BVSs) through stent implantation is common, yet the effectiveness of current BVS segmentation techniques from Intravascular Optical Coherence Tomography (IVOCT) images is inadequate. Methods: This paper introduces an enhanced segmentation approach using a novel Wavelet-based U-shape network to address these challenges. We developed a Wavelet-based U-shape network that incorporates an Attention Gate (AG) and an Atrous Multi-scale Field Module (AMFM), designed to enhance the segmentation accuracy by improving the differentiation between the stent struts and the surrounding tissue. A unique wavelet fusion module mitigates the semantic gaps between different feature map branches, facilitating more effective feature integration. Results: Extensive experiments demonstrate that our model surpasses existing techniques in key metrics such as Dice coefficient, accuracy, sensitivity, and Intersection over Union (IoU), achieving scores of 85.10%, 99.77%, 86.93%, and 73.81%, respectively. The integration of AG, AMFM, and the fusion module played a crucial role in achieving these outcomes, indicating a significant enhancement in capturing detailed contextual information. Conclusion: The introduction of the Wavelet-based U-shape network marks a substantial improvement in the segmentation of BVSs in IVOCT images, suggesting potential benefits for clinical practices in coronary artery disease treatment. This approach may also be applicable to other intricate medical imaging segmentation tasks, indicating a broad scope for future research.

Weak magnetic field promotes denitrification by stimulating ferromagnetic ion-containing metalloprotein expression.

Weak magnetic field (WMF) has been recognized to promote biological denitrification processes; however, the underlying mechanisms remain largely unexplored, hindering the optimization of its effectiveness. Here, we systematically investigated the effects of WMF on denitrification performance, enzyme activity, microbial community, and metaproteome in packed bed bioreactors treating high nitrate wastewater under different WMF intensities and C:N ratios. Results showed that WMFs significantly promoted denitrification by consistently stimulating the activities of denitrifying reductases and NAD+/NADH biosynthesis across decreasing C:N ratios. Reductases and electron transfer enzymes involved in denitrification were overproduced due to the significantly enriched overexpression of ferromagnetic ion-containing (FIC) metalloproteins. We also observed WMFs' intensity-dependent selective pressure on microbial community structures despite the effects being limited compared to those caused by changing C:N ratios. By coupling genome-centric metaproteomics and structure prediction, we found the dominant denitrifier, Halomonas, was outcompeted by Pseudomonas and Azoarcus under WMFs, likely due to its structural deficiencies in iron uptake, suggesting that advantageous ferromagnetic ion acquisition capacity was necessary to satisfy the substrate demand for FIC metalloprotein overproduction. This study advances our understanding of the biomagnetic effects in the context of complex communities and highlights WMF's potential for manipulating FIC protein-associated metabolism and fine-tuning community structure.

Associations of dietary selenium intake with the risk of chronic diseases and mortality in US adults.

Objective: Selenium is an essential micronutrient and a type of dietary antioxidant. This study aimed to investigate the associations of dietary selenium intake with the risk of human chronic disease [cardiovascular disease (CVD), diabetes mellitus (DM), and cancer] and mortality among US general adults. Methods: The dietary and demographic data in this study were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Death outcomes were determined by associating with the National Death Index (NDI) records as of December 31, 2019. Logistic regression analyses were used to investigate the relationship of selenium intake with the risk of CVD, DM, and cancer. The effect of dietary selenium on all-cause and disease-specific mortality was estimated with restricted cubic spline (RCS) curves based on the univariate and multivariate Cox proportional hazard models. Results: Among the 25,801 participants, dietary selenium intake was divided into quintiles (Q1-Q5). After covariate adjustment, the results showed that the participants with higher quintiles (Q4 and Q5) of selenium intake tended to have a low risk of CVD (OR = 0.97, 95% CI: 0.96, 0.99; OR = 0.98, 95% CI: 0.97, 1.00, respectively). Moreover, the RCS curves showed a significant nonlinear association between selenium intake and the risk of all-cause (with a HR of 0.82, 95% CI: 0.68, 0.99) and DM-specific mortality (with the lowest HR of 0.30; 95% CI, 0.12-0.75). Furthermore, we conducted a subgroup analysis and found a negative correlation between the highest quartile of selenium intake and all-cause mortality among participants aged 50 and above (HR = 0.75, 95% CI: 0.60-0.93, p = 0.009). Conclusion: Our results indicated that a moderate dietary selenium supplement decreased the risk of CVD and displayed a nonlinear trend in association with the risk of all-cause and DM-specific mortality among US adults. In addition, we found that participants aged 50 and older may benefit from higher selenium intake. However, these findings still need to be confirmed through further mechanism exploration.

Iron metabolism and arthritis: Exploring connections and therapeutic avenues.

ABSTRACT: Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases.

Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids' biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.

Effects of flaxseed oil supplementation on metaphase II oocyte rates in IVF cycles with decreased ovarian reserve: a randomized controlled trial.

Background: This study was designed to explore the effects of flaxseed oil on the metaphase II (MII) oocyte rates in women with decreased ovarian reserve (DOR). Methods: The women with DOR were divided into a study group (n = 108, flaxseed oil treatment) and a control group (n = 110, no treatment). All patients were treated with assisted reproductive technology (ART). Subsequently, the ART stimulation cycle parameters, embryo transfer (ET) results, and clinical reproductive outcomes were recorded. The influencing factors affecting the MII oocyte rate were analyzed using univariate analysis and multivariate analysis. Results: Flaxseed oil reduced the recombinant human follicle-stimulating hormone (r-hFSH) dosage and stimulation time and increased the peak estradiol (E2) concentration in DOR women during ART treatment. The MII oocyte rate, fertilization rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate were increased after flaxseed oil intervention. The embryo implantation rate of the study group was higher than that of the control group (p = 0.05). Additionally, the female age [odds ratio (OR): 0.609, 95% confidence interval (CI): 0.52-0.72, p < 0.01] was the hindering factor of MII oocyte rate, while anti-Müllerian hormone (AMH; OR: 100, 95% CI: 20.31-495, p < 0.01), peak E2 concentration (OR: 1.00, 95% CI: 1.00-1.00, p = 0.01), and the intake of flaxseed oil (OR: 2.51, 95% CI: 1.06-5.93, p = 0.04) were the promoting factors for MII oocyte rate. Conclusion: Flaxseed oil improved ovarian response and the quality of oocytes and embryos, thereby increasing the fertilization rate and high-quality embryo rate in DOR patients. The use of flaxseed oil was positively correlated with MII oocyte rate in women with DOR. Clinical trial number: https://www.chictr.org.cn/, identifier ChiCTR2300073785.

Analysis of research trends (2014-2023) on oxidative stress and male fertility based on bibliometrics and knowledge graphs.

Background: Oxidative stress (OS) is considered one of the major factors affecting male fertility, and research in this field has seen constant growth year by year. Currently, around 700 relevant papers are published each year, with a trend of further growth. Therefore, this study systematically summarizes the literature published in the last decade from a bibliometric perspective, revealing the dynamic development of the field, identifying research hotspots, analyzing future trends, and providing reference for further research. Methods: Relevant literature on oxidative stress and male fertility was retrieved from the Web of Science Core Collection (WoSCC) database, covering the timespan from 2014 to 2023 and including two types, articles and reviews. CiteSpace and VOSviewer were used for bibliometric analysis, including cluster analysis, co-occurrence analysis, co-citation analysis, and burst analysis of countries/regions, institutions, journals, authors, references, and keywords. Results: This paper studied a total of 5,301 papers involving 107 countries/regions, with China having the highest number of publications (898 papers) and the United States having the highest centrality (0.62). Burst analysis of journal citations revealed the emergence of many new journals (e.g., Antioxidants-Basel, Front Endocrinol) after 2021, indicating continuous expansion and development in this field. Cluster analysis of co-cited references and co-occurring keywords divided the research into areas such as oxidative stress and male infertility, oxidative stress level detection, and antioxidants. The keywords associated with research hotspots shifted from oxidative stress detection, sperm DNA damage, apoptosis, and redox potential to DNA methylation, embryonic development, infection, polyunsaturated fatty acids, and antioxidants. Conclusion: Bibliometric methods provide an intuitive reflection of the development process in the field of oxidative stress and male fertility, as well as the analysis of research hotspots in different periods. Research on oxidative stress and embryonic development, as well as antioxidant health management, may become hotspots in future research.

Bibliometric and Visual Analysis of the Research Status and Knowledge Structure of Assisted Reproductive Therapy for Patients with Premature Ovarian Insufficiency.

Objective: A large proportion of patients undergoing assisted reproductive therapy (ART) suffer from premature ovarian insufficiency (POI). The knowledge structure, research hotspots, and research trends related to ART for patients with POI are still unclear and have not been systematically summarized. We aimed to analyze the research status of ART for patients with POI and deeply explore its knowledge structure and research trends. Our findings may provide treatment recommendations for clinicians and guidance for researchers in further research. Methods: The PubMed database for publications on ART for patients with POI was searched. The Bibliographic Item Co-occurrence Matrix Builder (BICOMB) obtained the Co-word matrix and co-occurrence matrix. The H-index method was used to extract high-frequency main Medical Subject Headings (MeSH) terms/subheadings. Then we used software such as graphical clustering toolkit (gCluto), Microsoft Excel, Ucinet and NetDraw to carry out the biclustering analysis, strategic diagram analysis and social network analysis of the major MeSH terms/subheadings. Results: The high-frequency major MeSH terms/subheadings were analyzed by biclustering, strategic diagram, and social network analyses. A total of 431 articles from 1983 to 2023 were retrieved. Analysis showed that a total of 176 journals published relevant papers, including FERTILITY AND STERILITY, ranking first. In addition, we extracted 20 high-frequency major MeSH terms/subheadings. We grouped them into five categories: cryopreservation of oocyte and ovarian tissue, oocyte donation, in vitro activation (IVA) of primordial follicles, overview of therapy for patients with POI, therapy of iatrogenic POI. Within these five categories, there were 4, 4, 3, 4, and 5 major MeSH terms/subheadings, respectively. The major MeSH terms/subheadings were evenly distributed, and no particular group had a particular central tendency. Conclusion: The therapy of Iatrogenic POI is in the core position of research and is becoming increasingly mature. Oocyte donation and IVA of primordial follicles are the trends of future research. This study is helpful to understand the current research status, knowledge structure, and research trends of ART for patients with POI, and provide reference for improving ART for patients with POI in the future. Our study may guide clinicians to apply more established research to treat patients, which may lead to better treatment outcomes for patients. At the same time, we also suggest that researchers can conduct research in the field of future research trends, which may lead to greater research results.

The Impact of Parental Preconception Body Mass Index on the Outcomes of in vitro Fertilization-Embryo Transfer and Newborns' Outcomes.

Objective: Associations between parental pre-pregnancy BMI in IVF/ICSI fresh embryo transfer cycles and neonatal outcomes were investigated through a retrospective analysis. Methods: A retrospective analysis of Couples who underwent IVF/ICSI fresh embryo transfer 1340 cycles from January 2019 to December 2021 was conducted in the Department of Reproductive Medicine of our hospital. Based on the preconception BMI of parents, they were divided into four groups: Group A (both father and mother with BMI < 25 kg/m²), Group B (father with BMI < 25 kg/m² and mother with BMI ≥ 25 kg/m²), Group C (father with BMI ≥ 25 kg/m² and mother with BMI < 25 kg/m²), and Group D (both father and mother with BMI ≥ 25 kg/m²). The differences in baseline characteristics, fertilization and embryo development, pregnancy outcomes, and neonatal outcomes were compared among the groups. Results: In the IVF cycles, Group A had a higher rate of normal fertilization compared to three other groups, Group A is significantly higher than Group D, with statistical significance (P < .05). In the ICSI cycles, there were no significant differences among the four groups regarding normal fertilization rate, day 3 high-quality embryo rate, blastocyst formation rate, and high blastocyst rate. Univariate and multivariate analysis results showed no significant differences in clinical pregnancy and live birth rates among the four groups. However, Group D had a significantly higher rate of preterm birth than other three groups, with statistical significance (P < .05). Conclusion: To achieve better clinical outcomes and neonatal outcomes, overweight or obese couples should lose weight before undergoing IVF/ICSI treatment.

Corrigendum: Association between endometrial blood and clinical outcome in frozen single blastocyst transfer cycles.

[This corrects the article DOI: 10.3389/fphys.2023.1113853.].

Outcome of Different Endometrial Preparation Protocols Prior to Frozen-Thawed Embryo Transfer on Pregnancy Outcomes in Women with Repeated Implantation Failure.

Aim: To compare the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles among women with repeated implantation failure (RIF) treated with various endometrial preparation protocols. Methods: A total of 605 women with RIF were retrospectively recruited between January 2017 and December 2020 from Northern Theater General Hospital. Patients were divided into natural cycles, hormone replacement therapy (HRT) cycles, depot gonadotropin-releasing hormone (GnRH) agonist-HRT, and endometrial scratching (ES) plus depot GnRH agonist-HRT. The primary endpoint was clinical pregnancy rate, while secondary endpoints included live birth rate and pain assessment. Results: Of the 605 recruited patients, 63 were undergoing natural cycles, 281 were treated with HRT cycles, 141 treated with depot GnRH agonist-HRT, and 120 treated with ES combined with depot GnRH agonist-HRT. There were significant differences among protocols on clinical pregnancy rate (P=0.029), while no significant difference was observed among protocols on live birth rates (P=0.108). Multivariate analyses suggested that HRT (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.28-0.89; P=0.019) and depot GnRH agonist-HRT (OR: 0.49; 95% CI: 0.27-0.91; P=0.021) cycles were associated with a lower clinical pregnancy rate as compared with natural cycles, while no significant difference between ES combined with depot GnRH agonist-HRT and natural cycles for clinical pregnancy rates (OR: 0.72; 95% CI: 0.38-1.36; P=0.313). Moreover, the HRT (OR: 0.70; 95% CI: 0.39-1.28; P=0.239), depot GnRH agonist-HRT (OR: 0.67; 95% CI: 0.35-1.29; P=0.229), and ES combined with depot GnRH agonist-HRT (OR: 1.11; 95% CI: 0.58-2.14; P=0.754) cycles had no significant effects on live birth rate as compared with natural cycles. A total of 87.50% patients treated with ES combined with depot GnRH agonist-HRT reported pain during the procedure. Conclusion: ES and depot GnRH agonists could be considered for RIF women with high-quality blastocysts, 14 days after verified transplantation failure.

Regulation on air temperature by residential area morphology: A case study in Xuzhou City, China.

Due to woodlands and farmlands being replaced by residential areas in cities, continuous urbanization resulting in frequent urban heat island effects, especially in summer when high temperature seriously threaten health and lives of citizens. Although scientists realized that reasonable residential area morphology could effectively regulate air temperature and improve microclimate, it is lack of air temperature regulation-oriented specifications and requirements on morphology of residential areas. In this study, we used three types of morphological parameters of 15 residential areas in Xuzhou City and air temperature data via field investigation to analyze air temperature regulation caused by residential area morphology. The results showed that key morphological parameters of residential areas were different in morning and afternoon. In morning, independent effects of mean building height, street aspect ratio, and complete aspect ratio contributed 15.4%, 7.3%, and 6.8%, while those of building density, sky view factor, and the ratio of building surface area to floor area were 21.1%, 23.1%, and 6.9% in afternoon, respectively. Threshold values of efficiency of morphological parameters of residential areas were different between morning and afternoon. There were significant correlations between some morphological parameters of residential area. The results could provide data support and methodological reference for residential areas design in Xuzhou and surrounding cities.

Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy in Patients With Metastatic Soft Tissue Sarcoma: A Phase 1 Nonrandomized Controlled Trial.

Importance: Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts. Objective: To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions. Design, Setting, and Participants: This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis was performed from August 2016 to September 2022. Interventions: Two doses of IT GLA-SE (5 µg and 10 µg for 8 weekly doses) were tested for safety in combination with concurrent radiotherapy of the injected lesion. Main Outcomes and Measures: Primary end points were safety and tolerability. Secondary and exploratory end points included local response rates as well as measurement of antitumor immunity with immunohistochemistry and T-cell receptor (TCR) sequencing of tumor-infiltrating and circulating lymphocytes. Results: Twelve patients (median [range] age, 65 [34-78] years; 8 [67%] female) were treated across the 2 dose cohorts. Intratumoral GLA-SE was well tolerated, with only 1 patient (8%) experiencing a grade 2 adverse event. All patients achieved local control of the injected lesion after 8 doses, with 1 patient having complete regression (mean regression, -25%; range, -100% to 4%). In patients with durable local response, there were detectable increases in tumor-infiltrating lymphocytes. In 1 patient (target lesion -39% at 259 days of follow-up), TCR sequencing revealed expansion of preexisting and de novo clonotypes, with convergence of numerous rearrangements coding for the same binding sequence (suggestive of clonal convergence to antitumor targets). Single-cell sequencing identified these same expanded TCR clones in peripheral blood after treatment; these T cells had markedly enhanced Tbet expression, suggesting TH1 phenotype. Conclusions and Relevance: In this nonrandomized controlled trial, IT GLA-SE with concurrent radiotherapy was well tolerated and provided more durable local control than radiotherapy alone. Patients with durable local response demonstrated enhanced IT T-cell clonal expansion, with matched expansion of these clonotypes in the circulation. Additional studies evaluating synergism of IT GLA-SE and radiotherapy with systemic immune modulation are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02180698.

Evaluation of allylestrenol for clinical pregnancies in patients treated with assisted reproductive techniques: a retrospective, propensity score matched, observational study.

BACKGROUND: Allylestrenol is an oral progestogen being increasingly used for luteal phase support in assisted reproductive techniques. However, evidence of the clinical efficacy of allylestrenol in luteal phase support is lacking. Dydrogesterone is a representative drug used for luteal phase support, the efficacy of which has been clinically confirmed. As such, we aimed to compare the effects of allylestrenol with the standard dydrogesterone on clinical pregnancy rates and pregnancy outcomes. METHODS: This retrospective study included 3375 assisted reproductive technique cycles using either allylestrenol or dydrogesterone between January 2015 and March 2020. Patients using either allylestrenol or dydrogesterone were matched in a 1:1 ratio using propensity scores. The primary outcomes were clinical pregnancy rate and pregnancy outcomes. RESULTS: No significant difference was found in the clinical pregnancy rate (53.5% vs. 53.2%, P = 0.928) and pregnancy outcomes (all P > 0.05) between allylestrenol and dydrogesterone. Compared with dydrogesterone, the use of allylestrenol significantly reduced the rate of biochemical pregnancies (6.4% vs. 11.8%, P < 0.001) and multiple gestation rate (16.8% vs. 26.3%, P = 0.001). Moreover, endometrial thickness, morphology, and blood flow were significantly improved by allylestrenol treatment (all P < 0.05). CONCLUSIONS: Allylestrenol exhibited similar effects on clinical pregnancy rates and pregnancy outcomes as dydrogesterone. Moreover, allylestrenol can significantly reduce the biochemical pregnancy rate and improve the endometrial receptivity.

The role of dietary fiber on preventing gestational diabetes mellitus in an at-risk group of high triglyceride-glucose index women: a randomized controlled trial.

BACKGROUND: Pregnant women with a high triglyceride-glucose (TyG) index during early pregnancy may increase the risk of gestational diabetes mellitus (GDM), and dietary fiber could play an important role in glucose and lipid metabolism. However, no trials have tested the effects of dietary fiber on preventing GDM in women with a high TyG index. This study aims to investigate whether GDM can be prevented by dietary fiber supplementation in women with a TyG index ≥8.5 during early pregnancy (<20 weeks). METHODS: A randomized clinical trial was performed among 295 women with a TyG index ≥8.5 before 20 weeks of gestation, divided into a fiber group (24 g dietary fiber powder/day) or a control group (usual care). The intervention was conducted from 20 to 24+6 gestational weeks, and both groups received guidance on exercise and diet. The primary outcomes were the incidence of GDM diagnosed by a 75 g oral glucose tolerance test at 25-28 gestational weeks, and levels of maternal blood glucose, lipids. Secondary outcomes include gestational hypertension, postpartum hemorrhage, preterm birth, and other maternal and neonatal complications. RESULTS: GDM occurred at 11.2% (10 of 89) in the fiber group, which was significantly lower than 23.7 (44 of 186) in the control group (P = 0.015). The mean gestational weeks increased dramatically in the fiber group compared with the control group (39.07 ± 1.08 vs. 38.58 ± 1.44 weeks, P = 0.006). The incidence of preterm birth was 2.3% (2 of 86) of women randomized to the fiber group compared with 9.4% (17 of 181) in the control group (P = 0.032). The concentrations of 2 h postprandial blood glucose showed statistically higher in the control group compared with the intervention group (6.69 ± 1.65 vs. 6.45 ± 1.25 mmol/L, P = 0.026). There were no other significant differences between groups in lipid profile values, or other secondary outcomes. CONCLUSION: An intervention with dietary fiber supplementation during pregnancy may prevent GDM and preterm birth in women with a TyG index ≥8.5 before 20 weeks of gestation.