Skeletal muscle index based on CT at the 12th thoracic spine level can predict osteoporosis and fracture risk: a propensity score-matched cohort study.

Background: Multiple studies have shown that skeletal muscle index (SMI) measured on abdominal computed tomography (CT) is strongly associated with bone mineral density (BMD) and fracture risk as estimated by the fracture risk assessment tool (FRAX). Although some studies have reported that SMI at the level of the 12th thoracic vertebra (T12) measured on chest CT images can be used to diagnose sarcopenia, it is regrettable that no studies have investigated the relationship between SMI at T12 level and BMD or fracture risk. Therefore, we further investigated the relationship between SMI at T12 level and FRAX-estimated BMD and fracture risk in this study. Methods: A total of 349 subjects were included in this study. After 1∶1 propensity score matching (PSM) on height, weight, hypertension, diabetes, hyperlipidemia, hyperuricemia, body mass index (BMI), age, and gender, 162 subjects were finally included. The SMI, BMD, and FRAX score of the 162 participants were obtained. The correlation between SMI and BMD, as well as SMI and FRAX, was assessed using Spearman rank correlation. Additionally, the effectiveness of each index in predicting osteoporosis was evaluated through the receiver operating characteristic (ROC) curve analysis. Results: The BMD of the lumbar spine (L1-4) demonstrated a strong correlation with SMI (r = 0.416, p < 0.001), while the BMD of the femoral neck (FN) also exhibited a correlation with SMI (r = 0.307, p < 0.001). SMI was significantly correlated with FRAX, both without and with BMD at the FN, for major osteoporotic fractures (r = -0.416, p < 0.001, and r = -0.431, p < 0.001, respectively) and hip fractures (r = -0.357, p < 0.001, and r = -0.311, p < 0.001, respectively). Moreover, the SMI of the non-osteoporosis group was significantly higher than that of the osteoporosis group (p < 0.001). SMI effectively predicts osteoporosis, with an area under the curve of 0.834 (95% confidence interval 0.771-0.897, p < 0.001). Conclusion: SMI based on CT images of the 12th thoracic vertebrae can effectively diagnose osteoporosis and predict fracture risk. Therefore, SMI can make secondary use of chest CT to screen people who are prone to osteoporosis and fracture, and carry out timely medical intervention.

Performance on adsorption of toluene by ionic liquid-modified AC in high-humidity exhaust gas.

Volatile organic compounds (VOCs) frequently pose a threat to the biosphere, impacting ecosystems, flora, fauna, and the surrounding environment. Industrial emissions of VOCs often include the presence of water vapor, which, in turn, diminishes the adsorption capacity and efficacy of adsorbents. This occurs due to the competitive adsorption of water vapor, which competes with target pollutants for adsorption sites on the adsorbent material. In this study, hydrophobic activated carbons (BMIMPF6-AC (L), BMIMPF6-AC (g), and BMIMPF6-AC-H) were successfully prepared using 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) to adsorb toluene under humidity environment. The adsorption performance and mechanism of the resulting ionic liquid-modified activated carbon for toluene in a high-humidity environment were evaluated to explore the potential application of ionic liquids as hydrophobic modifiers. The results indicated that BMIMPF6-AC-H exhibited superior hydrophobicity. The toluene adsorption capacity of BMIMPF6-AC-H was 1.53 times higher than that of original activated carbon, while the adsorption capacity for water vapor was only 37.30% of it at 27 °C and 77% RH. The Y-N model well-fitted the dynamic adsorption experiments. To elucidate the microscopic mechanism of hydrophobic modification, the Independent Gradient Model (IGM) method was employed to characterize the intermolecular interactions between BMIMPF6 and toluene. Overall, this study introduces a new modifier for hydrophobic modification of activated carbon, which could enhance the efficiency of activated carbon in treating industrial VOCs.

Evaluating eight indicators for identifying metabolic syndrome in Chinese and American adolescents.

BACKGROUND: Early intervention and diagnosis of Metabolic Syndrome (MetS) are crucial for preventing adult cardiovascular disease. However, the optimal indicator for identifying MetS in adolescent remains controversial. METHODS: In total,1408 Chinese adolescents and 3550 American adolescents aged 12-17 years were included. MetS was defined according to the modified version for adolescents based on Adult Treatment Panel III (NCEP-ATP III) criteria. Areas under the curve (AUC) and corresponding 95% confidence interval (95% CI) of 8 anthropometric/metabolic indexes, such as waist circumference (WC), body mass index (BMI), a body shape index (ABSI), waist triglyceride index (WTI), were calculated to illustrate their ability to differentiate MetS. Sensitivity analysis using the other MetS criteria was performed. RESULTS: Under the modified NCEP-ATP III criteria, WTI had the best discriminating ability in overall adolescents, with AUC of 0.922 (95% CI: 0.900-0.945) in Chinese and 0.959 (95% CI: 0.949-0.969) in American. In contrast, ABSI had the lowest AUCs. Results of sensitivity analysis were generally consistent for the whole Chinese and American population, with the AUC for WC being the highest under some criteria, but it was not statistically different from that of WTI. CONCLUSIONS: WTI had relatively high discriminatory power for MetS detection in Chinese and American adolescents, but the performance of ABSI was poor. IMPACT: While many studies have compared the discriminatory power of some anthropometric indicators for MetS, there are few focused on pediatrics. The current study is the first to compare the discriminating ability of anthropometric/metabolic indicators (WC, BMI, TMI, ABSI, WHtR, VAI, WTI, and TyG) for MetS in adolescents. WTI remains the optimal indicator in screening for MetS in adolescents. WC was also a simple and reliable indicator when screening for MetS in adolescents, but the performance of ABSI was poor. This study provides a theoretical basis for the early identification of MetS in adolescents by adopting effective indicators.

Transplanted MSCs promote alveolar bone repair via hypoxia-induced extracellular vesicle secretion.

OBJECT: Mesenchymal stem cell (MSC) therapy is a potential strategy for promoting alveolar bone regeneration. This study evaluated the effects and mechanisms of transplanted MSCs on alveolar bone repair. METHODS: Mouse alveolar bone defect model was treated using mouse bone marrow mesenchymal stem cell (BMSC) transplantation. The bone repair was evaluated by micro-CT and Masson staining. The conditioned medium of hypoxia-treated BMSCs was co-cultured with normal BMSCs in vitro to detect the regulatory effect of transplanted MSCs on the chemotactic and migratory functions of host cells. The mechanisms were investigated using Becn siRNA transfection and western blotting. RESULTS: BMSC transplantation promoted bone defect regeneration. The hypoxic microenvironment induces BMSCs to release multiple extracellular vesicle (EV)-mediated regulatory proteins that promote the migration of host stem cells. Protein array analysis, western blotting, GFP-LC3 detection, and Becn siRNA transfection confirmed that autophagy activation in BMSCs plays a key role during this process. CONCLUSION: The local hypoxic microenvironment induces transplanted MSCs to secrete a large number of EV-mediated regulatory proteins, thereby upregulating the migration function of the host stem cells and promoting alveolar bone defect regeneration. This process depends on the autophagy-related mechanism of the transplanted MSCs.

The dehydration-responsive protein PpFAS1.3 in moss Physcomitrium patens plays a regulatory role in lipid metabolism.

Moss plants appear in the early stages of land colonization and possess varying degrees of dehydration tolerance. In this study, a protein called PpFAS1.3 was identified, which contains a fasciclin 1-like domain and is essential for the moss Physcomitrium patens' response to short-term rapid dehydration. When the FAS1.3 protein was knocked out, leafyshoots showed a significant decrease in tolerance to rapid dehydration, resulting in accelerated water loss and increased membrane leakage. Phylogenetic analysis suggests that PpFAS1.3 and its homologous proteins may have originated from bacteria and are specifically found in non-vascular plants like mosses and liverworts. As a dehydration-related protein, FAS1.3 plays a significant role in regulating lipid metabolism, particularly in the synthesis of free fatty acids (FFA) and the metabolism of two phospholipids, PC and PA. This discovery highlights the close connection between PpFAS1.3 and lipid metabolism, providing new insights into the molecular mechanisms underlying plant adaptation to stresses.

The benefits of reflecting on gratitude received at home for leaders at work: Insights from three field experiments.

Expressions of gratitude by leaders tend to yield positive effects in the workplace. Leaders, however, are not solely bestowers of gratitude but also recipients of it. Although leaders are often studied for their influence on others in the workplace, it is crucial to acknowledge that they are also complete individuals with personal lives outside of work that can spill over and affect their feelings and leadership behaviors at work. To advance research on leadership and gratitude, we take a whole-person view of leaders to understand the interpersonal crossover and intrapersonal spillover of gratitude. By integrating the moral affect theory of gratitude and savoring interventions research, we investigate how an intervention involving reflecting on gratitude received from family members at home motivates leaders to be more helpful and empowering toward their followers at work. We studied these ideas across three daily field experiments with 103 full-time managers from high schools, 116 leader-follower dyads from a variety of industries, and 109 leaders across various industries. Our findings demonstrate that when leaders reflected on receiving gratitude from family members at home, they felt higher prosocial impact at home, which in turn fulfilled their basic daily needs, consequently motivating them to engage in more helping and empowering behavior toward their followers at work. We also found some evidence that leaders higher in trait negative affect benefited the least from reflecting on receiving gratitude at home. We discuss how our findings provide extensions to literatures on gratitude, leadership, and work-family issues. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mid-term results of a prospective study for aortic dissection with a gutter-plugging chimney stent graft.

OBJECTIVES: Our goal was to access early and mid-term outcomes of a gutter-plugging chimney stent graft for treatment of Stanford type B aortic dissections in the clinical trial Prospective Study for Aortic Arch Therapy with stENt-graft for Chimney technology (PATENCY). METHODS: Between October 2018 and March 2022, patients with Stanford type B aortic dissections were treated with the Longuette chimney stent graft in 26 vascular centres. The efficiency and the incidence of adverse events over 12 months were investigated. RESULTS: A total of 150 patients were included. The technical success rate was 99.33% (149/150). The incidence of immediate postoperative endoleak was 5.33% (8/150, type I, n = 6; type II, n = 1; type IV, n = 1) neurologic complications (stroke or spinal cord ischaemia); the 30-day mortality was 0.67% (1/150) and 1.33% (2/150), respectively. During the follow-up period, the median follow-up time was 11.67 (5-16) months. The patent rate of the Longuette graft was 97.87%. Two patients with type I endoleak underwent reintervention. The follow-up rate of the incidence of retrograde A type aortic dissection was 0.67% (1/150). There was no paraplegia, left arm ischaemia or stent migration. CONCLUSIONS: For revascularization of the left subclavian artery, the Longuette chimney stent graft can provide an easily manipulated, safe and effective endovascular treatment. It should be considered a more efficient technique to prevent type Ia endoleak. Longer follow-up and a larger cohort are needed to validate these results. CLINICAL TRIAL REGISTRY NUMBER: NCT03767777.

Chairside digital design and manufacturing method for children's band and loop space maintainers.

OBJECTIVES: This study proposes a chairside digital design and manufacturing method for band and loop space maintainers and preliminarily validates its clinical feasibility. METHODS: Clinical cases of 10 children requiring space maintenance caused by premature loss of primary teeth were collected. Intraoral scan data of the affected children were also collected to establish digital models of the missing teeth. Using a pediatric band and loop space maintainer design software developed by our research team, a rapid personalized design of band and loop structures was achieved, and a digital model of an integrated band and loop space maintainer was ultimately generated. A chairside space maintainer was manufactured through metal computer numerical control machining for the experimental group, whereas metal 3D printing in the dental laboratory was used for the control group. A model fitting assessment was conducted for the space maintainers of both groups, and senior pediatric dental experts were invited to evaluate the clinical feasibility of the space maintainers with regard to fit and stability using the visual analogue scale scoring system. Statistical analysis was also performed. RESULTS: The time spent in designing and manufacturing the 10 space maintainers of the experimental group was all less than 1 h. Statistical analysis of expert ratings showed that the experimental group outperformed the control group with regard to fit and stability. Both types of space maintainers met clinical requirements. CONCLUSIONS: The chairside digital design and manufacturing method for pediatric band and loop space maintainers proposed in this study can achieve same-day fitting of space maintainers at the first appointment, demonstrating good clinical feasibility and significant potential for clinical application.

Absolute monocyte counts could predict disease activity and secondary loss of response of patients with Crohn's disease treated with anti-TNF-α drug.

BACKGROUND: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. METHODS: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. RESULTS: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. CONCLUSION: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

Evaluation of ecotourism suitability based on AHP-GIS: Taking Xiaoxiangling area of the Giant Panda National Park and the surrounding communities as an example.

The primary goal of national parks is to protect ecological environment, but also with the functions of scientific research, education, and recreation. Aiming for the realization of universal sharing, we used the analytic hierarchy process (AHP) to construct an ecotourism suitability evaluation system by selecting four factors, including landscape resources, ecological environment carrying capacity, recreation utilization capacity and social condition, taking Xiaoxiangling area of Giant Panda National Park and the surrounding communities as an example. We evaluated the ecotourism suitability based on GIS, and conducted a questionnaire survey of tourists, to propose suggestions on the functional zoning in terms of ecotourism suitability and subjective choice preferences of tourists. The results showed that the ecotourism suitability of the evaluation area could be classified into five levels. The most suitable areas were located nearby the natural landscape resources and far away from the core conservation area, and the least suitable areas distributed at the edge of the core conservation area. According to the results of suitability analysis, the evaluation area was divided into suitable development area, moderate development area, and restricted development area. Combined with the tourist preferences, we divided the recreational activities in the evaluation area into seven activities, namely, ecotourism, eco-camping, science education, leisure vacation, agricultural and animal husbandry culture experience, eco-education, and mountain adventure. These findings could help provide suitable services for different tourists and offer reference for the ecotourism developmental planning of the Xiaoxiangling area of the Giant Panda National Park.

Ovarian serous carcinoma with stomach metastasis: a rare case report and literature review.

Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis. Based on the characteristics of the case, the two tumors were considered to be the same. After chemotherapy, a partial response was observed in the stomach and pelvic lesions, suggesting the effectiveness of the treatment. Through three treatments of recurrence, gastroscopy confirmed the stomach to be a metastatic site. Therefore, determining the primary source of advanced tumors is crucial in guiding treatment decisions. Clinicians must approach this comprehensively, relying on thorough evaluation and personal experience.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Health Technology Assessment: Evaluation of 7 Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus.

Purpose: This study provides a reference for healthcare organizations in the selection and rational use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition). Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, and Embase, drug labels, and clinical guidelines were searched for drug information. We systematically evaluated 7 GLP-1RAs marketed in China for safety, efficacy, economy, pharmacological properties, and other attributes using a percentage scoring method. Results: The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points). Conclusion: When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide.

SLC38A2 promotes cell proliferation and invasion by promoting glutamine metabolism in adenomyosis.

Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis.

Tumor-derived mesenchymal progenitor cell-related genes in the regulation of breast cancer proliferation.

Background: Breast cancer (BC) is one of the most common malignancies worldwide, and its development is affected in various ways by the tumor microenvironment (TME). Tumor-derived mesenchymal progenitor cells (MPCs), as the most important components of the TME, participate in the proliferation and metastasis of BC in several ways. In this study, we aimed to characterize the genes associated with tumor-derived MPCs and determine their effects on BC cells. Methods: Tumor-derived MPCs and normal breast tissue-derived mesenchymal stem cells (MSCs) were isolated from tissues specimens of patients with BC. We conducted culture and passage, phenotype identification, proliferation and migration detection, inflammatory factor release detection, and other experiments on isolated MPCs from tumors and MSCs from normal breast tissues. Three paired tumor-derived MPCs and normal breast tissue-derived MSCs were then subjected to transcriptome analysis to determine the expression profiles of the relevant genes, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to further confirm gene expression. Subsequently, the overexpression plasmids were transfected into tumor-derived MPCs, and the expression of various inflammatory factors of tumor-derived MPCs and their proliferation were characterized with a cell viability test reagent (Cell Counting Kit 8). Subsequently, the transfected tumor-derived MPCs were cocultured with BC cells using a conditioned medium coculture method to clarify the role of tumor-derived MSCs in BC. Results: Tumor-derived MPCs expressed stem cell characteristics including CD105, CD90, and CD73 and exhibited adipogenic and osteogenic differentiation in vitro. The proliferation of tumor-derived MPCs was significantly lower than that of normal breast tissue-derived MSCs, and the invasive metastatic ability was comparable; however, MPCs were found to release inflammatory factors such as interleukin 6 (IL-6) and transforming growth factor ß (TGF-ß). Transcriptome analysis showed that stomatin (STOM), collagen and calcium binding EGF domains 1 (CCBE1), and laminin subunit alpha 5 (LAMA5) were significantly upregulated in tumor-derived MPCs. Among them, STOM was highly expressed in tumor-derived MPCs, which mediated the slow proliferation of MPCs and promoted the proliferation of BC cells. Conclusions: STOM, CCBE1, and LAMA5 were highly expressed in tumor-derived MPCs, with STOM being found to retard the proliferation of MPCs but promote the proliferation of BC cells. There findings present new possibilities in targeted microenvironmental therapy for BC.

Characteristics of primary care practices by proportion of patients unvaccinated against SARS-CoV-2: a cross-sectional cohort study.

BACKGROUND: Variations in primary care practices may explain some differences in health outcomes during the COVID-19 pandemic. We sought to evaluate the characteristics of primary care practices by the proportion of patients unvaccinated against SARS-CoV-2. METHODS: We conducted a population-based, cross-sectional cohort study using linked administrative data sets in Ontario, Canada. We calculated the percentage of patients unvaccinated against SARS-CoV-2 enrolled with each comprehensive-care family physician, ranked physicians according to the proportion of patients unvaccinated, and identified physicians in the top 10% (v. the other 90%). We compared characteristics of family physicians and their patients in these 2 groups using standardized differences. RESULTS: We analyzed 9060 family physicians with 10 837 909 enrolled patients. Family physicians with the largest proportion (top 10%) of unvaccinated patients (n = 906) were more likely to be male, to have trained outside of Canada, to be older, and to work in an enhanced fee-for-service model than those in the remaining 90%. Vaccine coverage (≥ 2 doses of SARS-CoV-2 vaccine) was 74% among patients of physicians with the largest proportion of unvaccinated patients, compared with 87% in the remaining patient population. Patients in the top 10% group tended to be younger and live in areas with higher levels of ethnic diversity and immigration and lower incomes. INTERPRETATION: Primary care practices with the largest proportion of patients unvaccinated against SARS-CoV-2 served marginalized communities and were less likely to use team-based care models. These findings can guide resource planning and help tailor interventions to integrate public health priorities within primary care practices.

One-year results of the flowdynamics dense mesh stent for residual dissection after proximal repair of stanford type a or type b aortic dissection: a multicenter, prospective and randomized study.

OBJECTIVE: Negative remodeling of the distal aorta following proximal repair for acute aortic dissection has garnered growing attention. This clinical scenario has spurred the development of techniques and devices. A multicenter, prospective, and randomized controlled study was conducted with the aim of confirming the safety and effectiveness of a newly-designed flowdynamics dense mesh stent for the treatment of residual dissection after proximal repair. METHODS: Patients with nonchronic residual dissection affecting visceral branches were prospectively enrolled at three centers and randomly allocated to either the FDMS group or the control group. Primary endpoints encompassed all-cause and aortic-related mortality, while the patency of branch arteries is indeed a key focal metric. Morphological changes (diameter, area, and volume) were analyzed to demonstrate the therapeutic effect. RESULTS: 112 patients were recruited in the clinical trial, and 103 patients completed the 12-month follow-up. The rate of freedom from all-cause and aortic-related death in the FDMS group was 94.64% and 100%, respectively. All visceral branches remained patent. The FDMS group exhibited a substantial expansion in TL and a notable shrinkage in FL at the planes below renal arteries (ΔArea TL: FDMS vs. Control, 0.74±0.46 vs. 0.34±0.66 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.72±1.26 vs. -0.12±0.86 cm, P = 0.01) and 5 cm below renal arteries (ΔArea TL: FDMS vs. Control, 1.06±0.75 vs. 0.16±0.63 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.53±1.43 vs. -0.25±1.00 cm, P = 0.27). Meanwhile, the FDMS group demonstrated an increase of 22.55±11.14 cm3 in TL (P<0.001) and a corresponding reduction of 21.94±11.77 cm3 in FL (P=0.08). CONCLUSIONS: This newly-designed FDMS for endovascular repair of residual dissection following the proximal repair is demonstrated to be safe and effective at 12 months.

The highly selective and sensitive fluorescence probe for detection of copper (II) ions and its bioimaging in vitro and vivo.

We designed and developed the probe W-3 for detection of Cu2+. The results showed probe can selectively detect Cu2+, accompanied by noticeable color change. The probe can detect the Cu2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu2+, with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu2+ in vitro and vivo.