Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.

Strategies for the Isolation and Identification of Gastric Cancer Stem Cells.

Gastric cancer stem cells (GCSCs) originate from both gastric adult stem cells and bone marrow cells and are conspicuously present within the histological milieu of gastric cancer tissue. GCSCs play pivotal and multifaceted roles in the initiation, progression, and recurrence of gastric cancer. Hence, the characterization of GCSCs not only facilitates precise target identification for prospective therapeutic interventions in gastric cancer but also has significant implications for targeted therapy and the prognosis of gastric cancer. The prevailing techniques for GCSC purification involve their isolation using surface-specific cell markers, such as those identified by flow cytometry and immunomagnetic bead sorting techniques. In addition, in vitro culture and side-population cell sorting are integral methods in this context. This review discusses the surface biomarkers, isolation techniques, and identification methods of GCSCs, as well as their role in the treatment of gastric cancer.

An evidence-based breathing exercise intervention for chronic pain management in breast cancer survivors: A phase II randomized controlled trial.

OBJECTIVE: Explore the preliminary effects of a breathing exercise (BE) intervention on chronic pain among breast cancer survivors. METHODS: This two-parallel-arm, open-label pilot randomized controlled trial recruited 72 breast cancer survivors who were randomly allocated to either the control or intervention group (n = 36 each). Both groups received usual care and a pain information booklet, while the intervention group received 4 weeks of additional BE. The primary clinical outcome was measured using the Brief Pain Inventory (BPI), with secondary clinical outcomes measured by the Hospital Anxiety and Depression Scale (HADS), Quality of Life Patient/Cancer Survivor Version in Chinese (QOLCSV-C), and Functional Assessment of Cancer Therapy- Breast (FACT-B) immediately post-intervention and at 4-week follow-up. Both adjusted and unadjusted Generalized Estimating Equation models were utilized to assess the BE's potential effects, with safety assessed through participant self-report. RESULTS: Sixty-eight participants completed the study. Statistical significance was observed in BPI in both adjusted and unadjusted models at post-intervention and follow-up (p < 0.05). BE demonstrated positive effects on anxiety, depression and quality of life improvement across all measures and timepoints in both adjusted and unadjusted models (p < 0.05). The effect sizes were smaller in the adjusted model. Three mild transient discomforts were reported associated with BE practice including dizziness, tiredness and yawning, without requirement of medical treatment. No severe adverse events occurred. CONCLUSION: This BE intervention appears effective in alleviating chronic pain, anxiety and depression, and improving quality of life for breast cancer survivors. Fully powered large-scale studies are required to confirm its effects.

Harmonic Scalpel Versus Monopolar Electrotome in Endoscopic-Assisted Transaxillary Dual-Plane Augmentation Mammaplasty: A Retrospective Study in 122 Patients.

BACKGROUND: The transaxillary approach of breast augmentation is the most popular method in Asia, but longer period of recovery was observed in spite of the assistance of endoscope. OBJECTIVES: Introducing the ultrasonic dissection devices might be a solution to minimizing tisue damage thus relieving pain and shortening the period of recovery. METHOD: Between March 2020 and September 2022, we retrospectively reviewed the cases of 122 patients underwent endoscopic augmentation mammoplasty via the transaxillary approach using either the monopolar electrotome (ME) alone or assisted with Harmonic Scalpel (HS) in defining the retropectoral pocket and severing the pectoralis major muscle. RESULT: The total drainage volume was significantly lower in the HS group than ME group (74.33 ± 48.81 vs. 180.30 ± 125.10 mL; p < 0.0001). VAS score of the first 24 hour after surgery of the ME group was significantly higher than that of the HS group (6.10 ± 1.27 vs. 2.88 ± 1.29, p < 0.0001). Operation time in HS group was reduced compared to ME group (113.1 ± 14.46 mins vs. 131.3 ± 35.51 mins, p < 0.001). The duration of drainage placement (1.08 ± 0.27 vs. 2.72 ± 1.18 days) and hospital stay after surgery (3.08 ± 0.42 vs. 5.64 ± 2.78 days; p < 0.0001) were largely reduced in HS group. CONCLUSION: The assistance of Harmonic Scalpel significantly reduced total postoperative drainage, relieved pain and shortened operation time, length of drainage placement and hospital stay compared to using monopolar electrotome alone in endoscopic-assisted transaxillary dual-plane augmentation mammaplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acteoside alleviates blood-brain barrier damage induced by ischemic stroke through inhibiting microglia HMGB1/TLR4/NLRP3 signaling.

Ischemic stroke (IS) can cause severe harm, inducing oxidative stress, inflammation, and pyroptotic death. IS treatment efficacy remains limited, and microglia are important regulators of IS-related blood-brain barrier (BBB) damage. It is thus vital that new therapeutic agents capable of targeting microglia be identified to treat IS-related damage to the BBB. Acteoside (ACT), which is a compound derived from Cistanche tubulosa (Schenk) Wight., offers promising bioactivity, but its ability to protect against central nervous system injury remains to be documented. To clarify the protective benefits and mechanisms through which ACT can protect against damage to the BBB, a rat middle cerebral artery occlusion (MCAO) model system was herein employed. These in vivo analyses demonstrated that ACT was able to significantly reduce cerebral infarct size while improving their neurological scores and altering neurotrophic and inflammatory factor release. RNA sequencing and molecular docking studies highlighted the ability of ACT to exert its protective benefits via the HMGB1/TLR4/NLRP3 axis. Western immunoblotting and immunofluorescent staining for tight junction proteins additionally confirmed the ability of ACT to preserve BBB integrity. The underlying mechanisms were then explored with an oxygen-glucose deprivation (OGD) model in vitro with BV2 cells. This strategy thus confirmed that the ability of ACT to suppress microglial inflammatory and pyroptotic activity was HMGB1/TLR4/NLRP3 pathway-dependent. These data thus offer novel evidence that ACT can protect against IS-related damage to the BBB through the abrogation of inflammatory and pyroptotic activity, underscoring its promise as a novel lead compound for the therapeutic treatment of IS.

Salipaludibacillus daqingensis sp. nov., a moderately halophilic bacterium isolated from an oilfield.

A novel alkaliphilic, Gram-stain-positive, moderately halophilic, rod-shaped, endospore-forming, motile, facultatively anaerobic bacterium (DQ-9T) was isolated from a sediment sample collected from Daqing oilfield in China, and characterized by a polyphasic taxonomic approach. Strain DQ-9T formed yellow pigment and grew occurred at salinities of 1-12 % (w/v) NaCl (optimum, 8 %) and at 10-40 °C (optimum, 30-35 °C), at pH 7.5-10.5 (optimum, pH 9.0-9.5). It was catalase-positive, but oxidase-negative. Based on the analysis of 16S rRNA gene sequences, DQ-9T was classified into the genus Salipaludibacillus and exhibited the highest similarities (98.37 %) to Salipaludibacillus neizhouensis JSM 071004T. Digital DNA-DNA hybridization and average nucleotide identity values between strain DQ-9T and the most closely related strain, S. neizhouensis DSM 19794T, were determined to be 72.0 and 21.6 %, respectively. The polar lipids were constituted by diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The major fatty acids (>5 %) comprised anteiso-C15 : 0, anteiso-C17 : 0, iso-C17 : 0, iso-C15 : 0 and C16 : 0. The cell-wall peptidoglycan contained meso-diaminopimelic acid, and menaquinone-7 was identified as the primary respiratory quinone. The DNA G+C content was 37.5 mol%. Through chemotaxonomic, physiological, and biochemical characterization, strain DQ-9T could be clearly distinguished from the closest Salipaludibacillus species. Based on provided data, strain DQ-9T is proposed to represent a novel species, Salipaludibacillus daqingensis sp. nov., within the genus Salipaludibacillus. The type strain is DQ-9T (=ACCC 60415T=KCTC 33936T).

Application of multidisciplinary collaborative nursing with family care for enhanced recovery after surgery in children with inguinal hernia.

BACKGROUND: Perioperative nursing can reduce the stress reaction and improve the prognosis of children. AIM: To elucidate the influence of multidisciplinary collaborative nursing for enhanced recovery after surgery (ERAS) with family care in perioperative nursing children with an inguinal hernia and its impact on the prognosis. METHODS: The data of 100 children with inguinal hernia were retrospectively analyzed. The participants were divided into three groups according to different nursing methods: Groups A (n = 38), B (n = 32), and C (n = 30). Group A received multidisciplinary collaborative ERAS nursing combined with family care nursing; Group B received multidisciplinary collaborative nursing for ERAS; and Group C received routine nursing. The postoperative recovery results of the three groups were compared, including intraoperative blood loss and postoperative feeding time, time of getting out of bed, hospitalization time, and defecation time. Furthermore, the incidence of common complications was also compared between the three groups. RESULTS: There was less intraoperative blood loss in Groups A and B than in Group C (P < 0.05), and the time of getting out of bed and postoperative hospitalization and defecation times were also decreased in Group C (P < 0.05). There was no significant difference in postoperative feeding time among the three groups (P > 0.05). Each index had no statistical significance between Groups A and B (P > 0.05). The incidence of urinary retention, infection, hematoma, and hernia recurrence in Group A was less than that in Group C (P < 0.05). No significant difference was observed in the overall complication rate between Groups A and B and between Groups B and C (P > 0.05). CONCLUSION: The application of multidisciplinary collaborative nursing combined with family care in the perioperative care of children with an inguinal hernia for ERAS may promote postoperative rehabilitation for children and reduce the incidence of complications.

METTL3 Promotes the Growth and Invasion of Melanoma Cells by Regulating the lncRNA SNHG3/miR-330-5p Axis.

Accumulating evidence indicates that m6A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m6A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m6A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo, whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m6A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m6A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.

Review of Single Crystal Synthesis of 11 Iron-Based Superconductors.

The 11 system in the iron-based superconducting family has become one of the most extensively studied materials in the research of high-temperature superconductivity, due to their simple structure and rich physical properties. Many exotic properties, such as multiband electronic structure, electronic nematicity, topology and antiferromagnetic order, provide strong support for the theory of high-temperature superconductivity, and have been at the forefront of condensed matter physics in the past decade. One noteworthy aspect is that a high upper critical magnetic field, large critical current density and lower toxicity give the 11 system good application prospects. However, the research on 11 iron-based superconductors faces numerous obstacles, mainly stemming from the challenges associated with producing high-quality single crystals. Since the discovery of FeSe superconductivity in 2008, researchers have made significant progress in crystal growth, overcoming the hurdles that initially impeded their studies. Consequently, they have successfully established the complete phase diagrams of 11 iron-based superconductors, including FeSe1-xTex, FeSe1-xSx and FeTe1-xSx. In this paper, we aim to provide a comprehensive summary of the preparation methods employed for 11 iron-based single crystals over the past decade. Specifically, we will focus on hydrothermal, chemical vapor transport (CVT), self-flux and annealing methods. Additionally, we will discuss the quality, size, and superconductivity properties exhibited by single crystals obtained through different preparation methods. By exploring these aspects, we can gain a better understanding of the advantages and limitations associated with each technique. High-quality single crystals serve as invaluable tools for advancing both the theoretical understanding and practical utilization of high-temperature superconductivity.

Quality of life patient/cancer survivor version in Chinese cancer survivors: A validation study.

Objective: To validate the Chinese version of the Quality of Life (QoL) Patient/Cancer Survivor Version (QOLCSV-C) for measuring QoL in Chinese cancer survivors. Methods: The study followed a seven-step research practice guideline for cross-cultural research instrument validation study including translation, adaptation, and psychometric assessment. A forward- and backward-translation procedure was approached, followed by cultural adaptation and acceptability assessment. For its psychometric properties, its concurrent validity with the Functional Assessment of Cancer Therapy-General (FACT-G) was examined with correlation analysis. The internal consistency (Cronbach's alpha) and item-total and item-subtotal correlations of the QOLCSV-C were obtained. Factor analyses were conducted. Floor and ceiling effects and the discriminant performance of the selected variables on QOLCSV-C score were also examined. Results: The QOLCSV-C was translated from the 41-item QOLCSV with four domains: psychological, physical, spiritual and social well-being. The content validity was excellent (CVI â€‹= â€‹1.00). Time spent to complete the QOLCSV-C was about 10 â€‹min. The QOLCSV-C was found easy to use, appropriate in length, and reflective of their QoL. The strong correlation between QOLCSV-C and FACT-G indicates a satisfactory concurrent validity (Spearman's rho â€‹= â€‹0.765, P â€‹< â€‹0.001, n â€‹= â€‹205). The overall internal consistency of the QOLCSV-C (Cronbach's alpha â€‹= â€‹0.888) and the split-half reliability (Spearman-Brown r â€‹= â€‹0.918) were excellent. Most of the items show moderate to strong item-total correlation. The exploratory factor analysis revealed a four-factor solution, and confirmatory factor analysis has a satisfactory model fit with indicative items. None of the total scores of QOLCSV-C reveal the floor or ceiling effect. For discriminant performance, variables demonstrating significant between-group differences include sleep quality, pain, fatigue, nausea, physical health, and financial burden. Conclusions: The QOLCSV-C is a reliable and valid instrument for measuring the QoL in Chinese cancer survivors. Future studies can explore the factor structure, gender universal or specific items, and significant predictors of QoL of cancer survivors in different cultures.

Potential Role of EPSPS Mutations in the Resistance of Eleusine indica to Glyphosate.

Gene mutation is a basic evolutionary mechanism in plants under selection pressure of herbicides. Such mutation has pleiotropic effects on plant growth. We systemically investigated the effects of Pro106Leu (P106L), Pro106Ser (P106S), and Thr102Ile + Pro106Ser (TIPS) mutations on EPSPS functionality and fitness traits in Eleusine indica at the biochemical and physiological levels. The affinity of natural EPSPS for glyphosate was 53.8 times higher than that for phosphoenolpyruvate (PEP), as revealed by the dissociation constant; the constant decreased in both the P106L (39.9-fold) and P106S (46.9-fold) mutants but increased in the TIPS (87.5-fold) mutant. The Km (PEP) values of the P106L, P106S, and TIPS mutants were 2.4-, 0.7-, and 4.1-fold higher than that of natural EPSPS, corresponding to resistance levels of 2.5, 1.9, and 11.4, respectively. The catalytic efficiency values (maximum reaction rates) were 0.89-, 0.94-, and 0.26-fold higher than that of natural EPSPS. The levels of metabolites related to amino acids and nucleotides were significantly reduced in the mutated plants. The fitness costs were substantial for the biomass, total leaf area, seed number, and seedling emergence throughout the growth period in the plants with P106L and TIPS mutations. These results provide insights into EPSPS kinetics and their effect on plant growth.

Evolutionary game study on multi-agent value co-creation of service-oriented digital transformation in the construction industry.

The service-oriented digital transformation of the construction industry is a development trend of cross-border industrial integration and transformation and upgrading in the digital economy environment, and collaborative value creation among stakeholders is seen as a strategic imperative to promote this process. This study aims to achieve efficient collaborative value co-creation and accelerate the digital transformation process of the construction industry by exploring the collaborative strategies and evolution laws of value co-creators in the digital service ecosystem of the construction industry. Based on evolutionary game theory and methods, this paper analyzes the evolutionary stability strategies and conditions of each participant in the service-oriented value chain at different stages of the digital transformation of the construction industry. It is found that with the improvement of the level of digitalization, the degree of cooperation among game players continues to increase until a stable state of full cooperation is achieved. The initial willingness of the game players to cooperate accelerates the speed of the system's evolution to the stable state of full cooperation in the middle stage of digital transformation. Additionally, the improvement of the construction process digitalization level can subvert the evolution result of full non-coordination caused by a low initial willingness to cooperate. The research conclusions and corresponding countermeasures and suggestions can provide a strategic reference for the service-oriented digital transformation of the construction industry.

Family functioning and nicotine dependence among smoking fathers: a cross-sectional study.

BACKGROUND: Nicotine dependence is a significant public health issue, and understanding the factors associated with nicotine dependence in this population is crucial for developing effective interventions. This study examined the association between family functioning and nicotine dependence levels of smoking fathers based on the McMaster model of family functioning (MMFF), providing evidence for future interventions. METHODS: In this study, we selected fathers of first- to fifth-grade students from 10 pilot elementary schools in Qingdao whose families smoked. We used the Fagerstrom test to assess nicotine dependence and the Family Assessment Device to evaluate family functioning. We performed univariate analysis to compare differences among those with different levels of nicotine dependence, and we used an ordinal logistic regression analysis to investigate the influences related to nicotine dependence. RESULTS: This study included 874 smokers, with 78.5% having mild nicotine dependence, 11.7% having moderate dependence, and 9.84% having severe dependence. Univariate analysis showed that smokers with severe dependence had lower education levels, higher prevalence of chronic diseases, more frequent alcohol consumption, and poorer family functioning compared to those with mild to moderate dependence. Ordinal logistic regression analysis showed that poorer general functioning scores (OR = 1.087, 95% CI: 1.008-1.173, P = 0.030), poorer behavioral control (OR = 1.124, 95% CI: 1.026-1.232, P = 0.012), more quit attempts, frequent alcohol consumption, and longer smoking duration may be associated with a higher likelihood of developing severe nicotine dependence. The older age of starting smoking and higher education level may be associated with a lower likelihood of developing severe nicotine dependence. However, it is important to note that the cross-sectional nature of this study precludes the determination of causal relationships. CONCLUSIONS: This study finds that heavy nicotine dependence in smoking fathers is associated with risky behaviors and demographics such as longer smoking duration and frequent alcohol consumption. Targeted smoking cessation interventions are crucial for this group, taking these specific factors into consideration. Family functioning, particularly general functioning and behavioral control, may also be linked to nicotine dependence, indicating the need for further research in this area.

Microbiome-metabolomics analysis reveals the potential effect of verbascoside in alleviating cognitive impairment in db/db mice.

Cognitive impairment is the main central nervous system complication of diabetes, affecting the quality of life of patients. Herba Cistanche is a homologous plant widely used as a health food and therapeutic drug. Verbascoside, a signature component of Herba Cistanche, has anti-diabetic and neuroprotective effects. However, it is quickly metabolized by the gut microbiota, and the mechanism of its neuroprotection and improvement of learning and memory remains unclear. We investigated the effectiveness and potential mechanisms of verbascoside on cognitive dysfunction in db/db mice using a 16S rRNA microbiome and serum metabolomics approach. We found that 12-week treatment with verbascoside significantly inhibited insulin resistance, reduced blood glucose and lipids, and improved cognitive deficits. In addition, verbascoside increased the gut microbiota diversity, improved intestinal dysbiosis, attenuated intestinal barrier disruption, reduced the levels of inflammatory factors, regulated the expression of the metabolites associated with cognitive function, and enhanced the central insulin sensitivity and hippocampal synaptogenesis signaling. We revealed that verbascoside induced the enrichment of Alistipes, Roseburia, and Intestinimonas in the gut, suppressed the abundance of Escherichia-Shigella, increased the serum levels of gamma-aminobutyric acid, L-glutamic acid, and L-lysine, and decreased taurine expression. Finally, a strong association between gut microbes, serum metabolites, and cognitive performance affected by verbascoside was observed. Our research suggests that alterations in gut microbes/metabolites are involved in the development of diabetic cognitive dysfunction, which is alleviated by verbascoside in the db/db mice through restructuring the gut microbiota composition, ameliorating diabetic metabolic disorders, and attenuating pathological brain damage.

DAPL1 prevents epithelial-mesenchymal transition in the retinal pigment epithelium and experimental proliferative vitreoretinopathy.

Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a hallmark of the pathogenesis of proliferative vitreoretinopathy (PVR) that can lead to severe vision loss. Nevertheless, the precise regulatory mechanisms underlying the pathogenesis of PVR remain largely unknown. Here, we show that the expression of death-associated protein-like 1 (DAPL1) is downregulated in PVR membranes and that DAPL1 deficiency promotes EMT in RPE cells in mice. In fact, adeno-associated virus (AAV)-mediated DAPL1 overexpression in RPE cells of Dapl1-deficient mice inhibited EMT in physiological and retinal-detachment states. In a rabbit model of PVR, ARPE-19 cells overexpressing DAPL1 showed reduced ability to induce experimental PVR, and AAV-mediated DAPL1 delivery attenuated the severity of experimental PVR. Furthermore, a mechanistic study revealed that DAPL1 promotes P21 phosphorylation and its stabilization partially through NFκB (RelA) in RPE cells, whereas the knockdown of P21 led to neutralizing effects on DAPL1-dependent EMT inhibition and enhanced the severity of experimental PVR. These results suggest that DAPL1 acts as a novel suppressor of RPE-EMT and has an important role in antagonizing the pathogenesis of experimental PVR. Hence, this finding has implications for understanding the mechanism of and potential therapeutic applications for PVR.

Examining Real-World Adherence to Nusinersen for the Treatment of Spinal Muscular Atrophy Using Two Large US Data Sources.

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by progressive muscular atrophy and weakness. Nusinersen was the first treatment approved for SMA. Per the US label, the nusinersen administration schedule consists of three loading doses at 14-day intervals, a fourth loading dose 30 days later, and maintenance doses every 4 months thereafter. Using two large US databases, we evaluated real-world adherence to nusinersen with its unique dosing schedule among generalizable populations of patients with SMA. METHODS: Patients with SMA treated with nusinersen, likely to have complete information on date of treatment initiation, were identified in the Optum® de-identified electronic health records (EHR) database (7/2017-9/2019), and in the Merative™ MarketScan® Research Databases from commercial (1/2017-6/2020) and Medicaid claims (1/2017-12/2019). Baseline demographics, number of nusinersen administrations on time, and distribution of inter-dose intervals were summarized. RESULTS: Totals of 67 and 291 patients were identified in the EHR and claims databases, respectively. Most nusinersen doses were received on time (93.9% EHR, 80.5% claims). Adherence was higher during the maintenance phase (90.6%) than the loading phase (71.1%) in the claims analysis, in contrast with the EHR analysis (95.5% and 92.6%, respectively), suggesting that not all loading doses of nusinersen may be accurately captured in claims. Inter-dose intervals captured in both databases aligned with the expected dosing schedule. CONCLUSION: Most nusinersen doses were received on time, consistent with the recommended schedule. Our findings also highlight the importance of careful methodological approaches when using real-world administrative databases for evaluation of nusinersen treatment patterns.

Adherence to medicines in the real world is important for patients with chronic disease to see long-term benefits of treatment. This study shows the importance and challenges of measuring adherence using real-world administrative data sources. This is especially important for drugs given through lumbar puncture with unique dosing schedules, such as nusinersen for the treatment of spinal muscular atrophy. In this study, most patients with spinal muscular atrophy received their nusinersen doses on time.

Bifurcation analysis of a sheep brucellosis model with testing and saturated culling rate.

Testing-culling is a very effective measure for the prevention and control of animal diseases. In this paper, based on sheep brucellosis control policies and animal testing characteristics and considering the limitation of culling resources, a dynamic model is established to study the impact of testing-culling measure. Theoretical analysis reveals that the model may have one or three positive equilibria. The equilibrium in the middle is always unstable, and the model shows saddle-node bifurcation, generalized Hopf bifurcation and Bogdanov-Takens bifurcation. Moreover, the theoretical results are verified via numerical analysis. These results reveal that testing and culling strategies can induce complex transmission dynamics that can help us develop appropriate prevention and control measures for animal brucellosis.

Development and Validation of an Evidence-Based Breathing Exercise Intervention Protocol for Chronic Pain Management in Breast Cancer Survivors.

BACKGROUND: Breathing exercise has been utilized as a promising approach to pain management in cancer survivors. However, the development process of the breathing exercise intervention protocol was rarely reported. AIM: To develop an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors and to provide a detailed account of the intervention development process. METHODS: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention. The breathing exercise intervention development process adopted phase one of the Medical Research Council Framework for Developing and Evaluating Complex Intervention framework. The content validity index was applied to determine the consensus of the appropriateness of the breathing exercise intervention protocol among the panel experts. RESULTS: The preliminary breathing exercise intervention protocol was developed based on fight-or-flight theory and vagus nerve theory, and the best available research evidence identified from seven systematic reviews, three clinical trials, and four practice recommendations. The breathing exercise intervention was designed as slow deep pursed-lip breathing with a time ratio of inspiration to expiration 1:2-3. The intensity of the breathing exercise was determined as 3 to 5 sessions a day, 5 minutes per session, for 4 weeks. The content validity of the breathing exercise intervention protocol was excellent as consensus was achieved among all panel experts with both the item-level and scale-level CVIs reaching 1.0. CONCLUSIONS: This study developed an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors. The protocol is well-supported by the relevant theories, research evidence, practice recommendations, and experts' consensus.

Feasibility and potential effects of breathing exercise for chronic pain management in breast cancer survivors: study protocol of a phase II randomised controlled trial.

INTRODUCTION: Chronic pain is a common symptom significantly affecting the quality of life of breast cancer survivors. Despite the achievement of pharmacological interventions, the barriers associated with this approach such as inaccessibility, misuse and side effects drive research into effective non-pharmacological interventions to improve chronic pain management, quality of life, anxiety and depression. Breathing exercise (BE) can be a promising option, but research evidence is sparse. This pilot study aims to examine the feasibility and preliminary effect of using an evidence-based BE intervention for chronic pain management in breast cancer survivors. METHOD AND ANALYSIS: This study will be a two-parallel-arm, open-labelled, phase II randomised controlled trial with 1:1 allocation. Seventy-two participants will be recruited from a tertiary hospital in China and randomly allocated to either a BE intervention group (n=36) or a control group (n=36). The participants in the intervention group will receive the usual care, a pain information booklet and a 4-week self-administered BE intervention; the participants in the control group will receive the usual care and the pain information booklet only. The assessment will be conducted at three time points: baseline (week 0), immediately after the intervention completion (week 5) and 4 weeks after the intervention completion (week 9). The primary outcomes will be the acceptability and feasibility assessment of the study protocol and methodological procedures. The secondary outcomes will be the effects of BE on pain, quality of life, anxiety and depression in breast cancer survivors. Descriptive statistics will be applied to present the primary outcomes and the Generalised Estimating Equation Model will be utilised to analyse the clinical outcomes. ETHICS AND DISSEMINATION: This study has received ethical approvals from the Human Research Ethics Committee at Charles Darwin University (H21089) and the Clinical Trial Ethics Committee at the Affiliated Hospital of Southwest Medical University (KY2022107). Findings from this study will be presented at academic conferences and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05257876.

Discovery of a Novel Bloom's Syndrome Protein (BLM) Inhibitor Suppressing Growth and Metastasis of Prostate Cancer.

Prostate cancer (PCa) is a common cancer and a major cause of cancer-related death worldwide in men, necessitating novel targets for cancer therapy. High expression of Bloom's syndrome protein (BLM) helicase is associated with the occurrence and development of PCa. Therefore, the identification and development of new BLM inhibitors may be a new direction for the treatment of PCa. Here, we identified a novel inhibitor by molecular docking and put it to systematic evaluation via various experiments, AO/854, which acted as a competitive inhibitor that blocked the BLM-DNA interaction. Cellular evaluation indicated that AO/854-suppressed tumor growth and metastasis in PC3 cells by enhancing DNA damage, phosphorylating Chk1/Chk2, and altering the p53 signaling pathway. Collectively, the study highlights the potential of BLM as a therapeutic target in PCa and reveals a distinct mechanism by which AO/854 competitively inhibits the function of BLM.