Dose rate correction for the novel 2D diode array MapCHECK 3.

PURPOSE: To investigate the dose rate dependence of MapCHECK3 and its influence on measurement accuracy, as well as the effect of dose rate correction. MATERIALS AND METHODS: The average and instantaneous dose rate dependence of MapCHECK2 and MapCHECK3 were studied. The accuracy of measurements was investigated where the dose rate differed significantly between dose calibration of the MapCHECK and the measurement. Measurements investigated include: the central axis dose for different fields at different depths, off-axis doses outside the field, and off-axis doses along the wedge direction. Measurements using an ion chamber were taken as the reference. Exponential functions were fit to account for average and instantaneous dose rate dependence for MapCHECK3 and used for dose rate correction. The effect of the dose rate correction was studied by comparing the differences between the measurements for MapCHECK (with and without the correction) and the reference. RESULTS: The maximum dose rate dependence of MapCHECK3 is greater than 2.5%. If the dose calibration factor derived from a 10 × 10 cm2 open field at 10 cm depth was used for measurements, the average differences in central diode dose were 0.8% ± 1.0% and 1.0% ± 0.8% for the studied field sizes and measurement depths, respectively. The introduction of wedge would not only induce -1.8% ± 1.3% difference in central diode dose, but also overestimate the effective wedge angle. After the instantaneous dose rate correction, above differences can be changed to 1.9% ± 8.1%, 0.2% ± 0.1%, and 0.0% ± 0.9%. The pass rate can be improved from 98.4% to 98.8%, 98.3%-100.0%, and 96.3%-100.0%, respectively. CONCLUSION: Compared with MapCHECK2 (SunPoint1 diodes), the more pronounced dose rate dependence of MapCHECK3 (SunPoint2 diodes) should be carefully considered. To ensure highly accurate measurement, it is suggested to perform the dose calibration at the same condition where measurement will be performed. Otherwise, the dose rate correction should be applied.

Physical literacy-based intervention for older adults: a cluster randomized controlled trial study protocol.

The ageing population creates concerns and challenges worldwide. The large number of older adults (aged over 65) in Hong Kong continues to rise as people live longer. This may result in heavy burdens on public services and problems such as a shortage of medical resources. The purpose of this study is to implement a physical literacy-based intervention among older adults in Hong Kong in order to achieve the goal of health promotion. A two-arm cluster randomized controlled trial will be employed in this proposed study. Ten daycare centers for the older adults in Hong Kong will be invited to participate in this study. The intervention group will receive functional fitness training and mastering physical literacy class twice a week with buddy peer support, and they will be asked to keep a reflective writing journal on a daily basis for 12 weeks in total. Participants will be evaluated at baseline (week 0), post-intervention (week 12), and at 6-week follow-up (week 18). This will consist of objective and self-reported measures covering elements within physical literacy (i.e., physical competence, motivation and confidence, knowledge and understanding) and also physical activity levels on an individual basis. The study intends to introduce a conceptual framework of physical literacy for the older adults through an intervention that allows older people to develop daily behaviour habits, which should promote active ageing for the older adults and greater self-esteem in later life. After this study, participants may share their positive experiences, and encourage their peers in the community to become physically literate in the future. In the long run, due to the feasibility and sustainability of these potential programs, this proposed study has the potential to connect seniors through social engagement and contribute to healthy living. Clinical trial approval from the National Library of Medicine (Reference number: NCT06137859).

A Perspective on Evaluating Life Stage Differences in Drug Dosages for Drug Labeling and Instructions.

Drug labeling and instructions provide essential information for patients regarding the usage of drugs. Instructions for the dosage of drug usage are critical for the effectiveness of the drug and the safety of patients. The dosage of many drugs varies depending on the patient's age. However, as our understanding of human biology deepens, we believe that these instructions need to be modified to incorporate different life stages. This is because human biology and metabolism differ significantly among different life stages, and their responses to drugs also vary. Additionally, the same age of different persons may fall into different life stages. Therefore, our group from multiple institutes and countries proposes a reexamination of whether incorporating life stages in all or any drug instructions will greatly enhance drug efficiency and patients' health.

Paeoniflorin Promotes Ovarian Development in Mice by Activating Mitophagy and Preventing Oxidative Stress.

During the development of animal organs, various adverse stimuli or toxic environments can induce oxidative stress and delay ovarian development. Paeoniflorin (PF), the main active ingredient of the traditional Chinese herb Paeonia lactiflora Pall., has protective effects on various diseases by preventing oxidative stress. However, the mechanism by which PF attenuates oxidative damage in mouse ovaries remains unclear. We evaluated the protective effects of PF on ovaries in an H2O2-induced mouse oxidative stress model. The H2O2-induced mouse ovarian oxidative stress model was used to explore the protective effect of PF on ovarian development. Histology and follicular development were observed. We then detected related indicators of cell apoptosis, oxidative stress, and autophagy in mouse ovaries. We found that PF inhibited H2O2-induced ovarian cell apoptosis and ferroptosis and promoted granulosa cell proliferation. PF prevented oxidative stress by increasing nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression levels. In addition, the autophagic flux of ovarian cells was activated and was accompanied by increased lysosomal biogenesis. Moreover, PF-mediated autophagy was involved in clearing mitochondria damaged by H2O2. Importantly, PF administration significantly increased the number of primordial follicles, primary follicles, secondary follicles, and antral follicles. PF administration improved ovarian sizes compared with the H2O2 group. The present study suggested that PF administration reversed H2O2-induced ovarian developmental delay and promoted follicle development. PF-activated mitophagy is crucial for preventing oxidative stress and improving mitochondrial quality.

Abandonment of prescriptions in medically underserved areas: Primary medication non-adherence in community pharmacies in the delta region of the United States.

Background: In the U.S. alone, medication non-adherence is estimated to cause 1 in 10 hospitalizations, approximately 125,000 deaths annually, and cost the U.S. healthcare system just under $300 billion each year. Patients in medically underserved areas (MUAs) are particularly vulnerable to all forms of non-adherence and downstream morbidity and mortality; however, the extent to which primary medication non-adherence (i.e., prescription abandonment) affects the underserved is still largely unknown. Objectives: To assess the difference in rates of abandonment of quality measured prescriptions in areas that are medically underserved compared to areas that are not. The secondary objective is to assess the impact that the COVID-19 pandemic had on rates of prescription abandonment in both MUAs and those that are not. Methods: In this retrospective study, data on abandoned, quality measured prescriptions were collected and analyzed using Chi-Square analyses from one regional division of a large grocery-chain pharmacy containing ninety-one pharmacies located in Tennessee, Mississippi, Arkansas, Kentucky, and Missouri. The primary objective used 2019 data while the secondary objective used data from April - November of both 2019 and 2020. Results: Patients from MUAs abandoned quality measured prescriptions at a higher rate of 5.44% compared to 4.77% of those not living in these areas (P < 0.01). This study also discovered that during the COVID-19 pandemic, MUAs had a decrease in abandonment from 6.14% in 2019 to 6.02% in 2020 (P < 0.01). Those from non-MUAs had non-significant change in abandonment (P = 0.87). Conclusion: Patients in MUAs abandon quality measured prescriptions at a statistically significant higher rate when compared to patients who live in areas that are not considered to be medically underserved. Moreover, during the COVID-19 pandemic patients living in MUAs had a statistically significant decrease in prescription abandonment while those in non-MUAs did not statistically change.

Cinnamaldehyde activates AMPK/PGC-1α pathway via targeting GRK2 to ameliorate heart failure.

BACKGROUND: According to recent research, treating heart failure (HF) by inhibiting G protein-coupled receptor kinase 2 (GRK2) to improve myocardial energy metabolism has been identified as a potential approach. Cinnamaldehyde (CIN), a phenylpropyl aldehyde compound, has been demonstrated to exhibit beneficial effects in cardiovascular diseases. However, whether CIN inhibits GRK2 to ameliorate myocardial energy metabolism in HF is still unclear. PURPOSE: This study examines the effects of CIN on GRK2 and myocardial energy metabolism to elucidate its underlying mechanism to treat HF. METHODS: The isoproterenol (ISO) induced HF model in vivo and in vitro were constructed using Sprague-Dawley (SD) rats and primary neonatal rat cardiomyocytes (NRCMs). Based on this, the effects of CIN on myocardial energy metabolism and GRK2 were investigated. Additionally, validation experiments were conducted after interfering and over-expressing GRK2 in ISO-induced NRCMs to verify the regulatory effect of CIN on GRK2. Furthermore, binding capacity between GRK2 and CIN was explored by Cellular Thermal Shift Assay (CETSA) and Microscale Thermophoresis (MST). RESULTS: In vivo and in vitro, CIN significantly improved HF as demonstrated by reversing abnormal changes in myocardial injury markers, inhibiting myocardial hypertrophy and decreasing myocardial fibrosis. Additionally, CIN promoted myocardial fatty acid metabolism to ameliorate myocardial energy metabolism disorder by activating AMPK/PGC-1α signaling pathway. Moreover, CIN reversed the inhibition of myocardial fatty acid metabolism and AMPK/PGC-1α signaling pathway by GRK2 over-expression in ISO-induced NRCMs. Meanwhile, CIN had no better impact on the stimulation of cardiac fatty acid metabolism and the AMPK/PGC-1α signaling pathway in ISO-induced NRCMs when GRK2 was disrupted. Noticeably, CETSA and MST confirmed that CIN binds to GRK2 directly. The binding of CIN and GRK2 promoted the ubiquitination degradation of GRK2 mediated by murine double mimute 2. CONCLUSION: This study demonstrates that CIN exerts a protective intervention in HF by targeting GRK2 and promoting its ubiquitination degradation to activate AMPK/PGC-1α signaling pathway, ultimately improving myocardial fatty acid metabolism.

The role of gut microbiota in MP/NP-induced toxicity.

Microplastics (MPs) and nanoplastics (NPs) are globally recognized as emerging environmental pollutants in various environmental media, posing potential threats to ecosystems and human health. MPs/NPs are unavoidably ingested by humans, mainly through contaminated food and drinks, impairing the gastrointestinal ecology and seriously impacting the human body. The specific role of gut microbiota in the gastrointestinal tract upon MP/NP exposure remains unknown. Given the importance of gut microbiota in metabolism, immunity, and homeostasis, this review aims to enhance our current understanding of the role of gut microbiota in MP/NP-induced toxicity. First, it discusses human exposure to MPs/NPs through the diet and MP/NP-induced adverse effects on the respiratory, digestive, neural, urinary, reproductive, and immune systems. Second, it elucidates the complex interactions between the gut microbiota and MPs/NPs. MPs/NPs can disrupt gut microbiota homeostasis, while the gut microbiota can degrade MPs/NPs. Third, it reveals the role of the gut microbiota in MP/NP-mediated systematic toxicity. MPs/NPs cause direct intestinal toxicity and indirect toxicity in other organs via regulating the gut-brain, gut-liver, and gut-lung axes. Finally, novel approaches such as dietary interventions, prebiotics, probiotics, polyphenols, engineered bacteria, microalgae, and micro/nanorobots are recommended to reduce MP/NP toxicity in humans. Overall, this review provides a theoretical basis for targeting the gut microbiota to study MP/NP toxicity and develop novel strategies for its mitigation.

Trehalose attenuates testicular aging by activating autophagy and improving mitochondrial quality.

BACKGROUND: Reproductive aging can adversely affect male fertility and the health of offspring. The aging process is accompanied by impaired autophagy. Recent studies have shown that Trehalose plays an important role in the prevention of various diseases by regulating autophagy. However, the roles of Trehalose in testicular aging and reproductive decline remain to be clarified. OBJECTIVE: The present study aimed to evaluate the protective effects of Trehalose on testes in an aging mouse model. MATERIALS AND METHODS: In this study, an in vivo aging model in mice by administering D-galactose was established to explore the protective effect of Trehalose on testicular aging. We examined histological changes and related indicators of apoptosis, autophagy, mitochondrial biogenesis, and sperm quality. RESULTS: D-galactose treatment induced oxidative stress, apoptosis, and impairment of autophagy of testicular cells in mouse testes. Trehalose administration significantly reduced germ cell apoptosis and DNA damage caused by D-galactose-induced oxidative stress. Notably, Trehalose activated autophagy activity and improved mitochondrial function in testicular cells. Furthermore, Trehalose treatment increased the expression level of the tight junction protein ZO-1, and accelerated clearance of damaged mitochondria in Sertoli cells, indicating that Trehalose ameliorated Sertoli cell function in D-galactose-induced aging testes. DISCUSSION AND CONCLUSION: These findings suggest that Trehalose administration activated the autophagy activity in testicular cells and improved mitochondrial function, thereby effectively preventing testicular aging. Trehalose and its activated autophagy are crucial for preventing testicular aging, thus restoring autophagy activity by administering Trehalose could be a promising means to delay aging.

Baicalein-modified chitosan nanofiber membranes with antioxidant and antibacterial activities for chronic wound healing.

Diabetic foot ulcers, burns and many other trauma can lead to the formation of skin wounds, which often remain open for a long period of time, seriously affecting the quality of patient's life. Oxidative stress and infection are the main factors affecting the healing of chronic wounds, so it is important to develop dressings with dual antioxidant and antimicrobial properties for wound management. In this study, functionalized chitosan was synthesized by modifying chitosan with antioxidant baicalein to enhance the antimicrobial and antioxidant activities of chitosan. Then the obtained baicalein-modified chitosan was prepared into nanofibrous membranes by electrospinning. The membrane structures were characterized, and the antioxidant and antibacterial activities were evaluated by in vivo and in vitro experiments. The results showed that the prepared wound dressings had excellent antioxidant and antibacterial activities and significantly accelerated the wound process. This study provided a reference for the development of novel dressing materials to promote wound healing.

Unleashing the potential of Li-O2 batteries with electronic modulation and lattice strain in pre-lithiated electrocatalysts.

Efficient catalysts are indispensable for overcoming the sluggish reaction kinetics and high overpotentials inherent in Li-O2 batteries. However, the lack of precise control over catalyst structures at the atomic level and limited understanding of the underlying catalytic mechanisms pose significant challenges to advancing catalyst technology. In this study, we propose the concept of precisely controlled pre-lithiated electrocatalysts, drawing inspiration from lithium electrochemistry. Our results demonstrate that Li+ intercalation induces lattice strain in RuO2 and modulates its electronic structure. These modifications promote electron transfer between catalysts and reaction intermediates, optimizing the adsorption behavior of Li-O intermediates. As a result, Li-O2 batteries employing Li0.52RuO2 exhibit ultrahigh energy efficiency, long lifespan, high discharge capacity, and excellent rate performance. This research offers valuable insights for the design and optimization of efficient electrocatalysts at the atomic level, paving the way for further advancements in Li-O2 battery technology.

Comprehensive analysis of the association between triglyceride-glucose index and coronary artery disease severity across different glucose metabolism states: a large-scale cross-sectional study from an Asian cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research. METHODS: This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings. RESULTS: Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22-1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3-2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications. CONCLUSIONS: The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients.

Applying the six-sigma methodology to determine the limits of quality control (QC) tests for a specific linear accelerator.

PURPOSE: We aimed to show the framework of the six-sigma methodology (SSM) that can be used to determine the limits of QC tests for the linear accelerator (Linac). Limits for QC tests are individually determined using the SSM. METHODS AND MATERIALS: The SSM is based on the define-measure-analyze-improve-control (DMAIC) stages to improve the process. In the "define" stage, the limits of QC tests were determined. In the "measure" stage, a retrospective collection of daily QC data using a Machine Performance Check platform was performed from January 2020 to December 2022. In the "analyze" stage, the process of determining the limits was proposed using statistical analyses and process capability indices. In the "improve" stage, the capability index was used to calculate the action limits. The tolerance limit was established using the larger one of the control limits in the individual control chart (I-chart). In the "control" stage, daily QC data were collected prospectively from January 2023 to May 2023 to monitor the effect of action limits and tolerance limits. RESULTS: A total of 798 sets of QC data including beam, isocenter, collimation, couch, and gantry tests were collected and analyzed. The Collimation Rotation offset test had the min-Cp, min-Cpk, min-Pp, and min-Ppk at 2.53, 1.99, 1.59, and 1.25, respectively. The Couch Rtn test had the max-Cp, max-Cpk, max-Pp, and max-Ppk at 31.5, 29.9, 23.4, and 22.2, respectively. There are three QC tests with higher action limits than the original tolerance. Some data on the I-chart of the beam output change, isocenter KV offset, and jaw X1 exceeded the lower tolerance and action limit, which indicated that a system deviation occurred and reminded the physicist to take action to improve the process. CONCLUSIONS: The SSM is an excellent framework to use in determining the limits of QC tests. The process capability index is an important parameter that provides quantitative information on determining the limits of QC tests.

Environmental judicial reform and corporate investment behavior - Based on a quasi-natural experiment of environmental courts.

Ensuring the effectiveness of environmental legislation and regulations necessitates enhancing the professional caliber of the environmental judiciary. Utilizing a multi-period difference-in-differences model, we explore the impact of environmental judicial reforms, exemplified by the establishment of environmental courts, on corporate investment behavior. We find that firms in regions with established environmental courts significantly increase their environmental investments and productive investments, while financial investments remain unaffected. Mechanism testing reveals that the environmental court affects corporate investment by strengthening local government environmental enforcement and promoting public environmental participation. Furthermore, the marginal effect of environmental courts is more pronounced in regions with fewer environmental regulations and lower economic development levels, as well as in state-owned enterprises. Compared to collegiate benches, environmental resources judicial tribunals exert a greater influence on corporate investment behavior. This study adds to the micro-economic analysis of environmental judiciary by providing empirical evidence on how formal institutional frameworks impact corporate investment behavior.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Anti-atherosclerotic effect of tetrahydroxy stilbene glucoside via dual-targeting of hepatic lipid metabolisms and aortic M2 macrophage polarization in ApoE-/- mice.

Tetrahydroxy stilbene glucoside (TSG) is a water-soluble natural product that has shown potential in treating atherosclerosis (AS). However, its underlying mechanisms remain unclear. Here, we demonstrate that an 8-week TSG treatment (100 mg/kg/d) significantly reduces atherosclerotic lesions and alleviates dyslipidemia symptoms in ApoE-/- mice. 1H nuclear magnetic resonance metabolomic analysis reveals differences in both lipid components and water-soluble metabolites in the livers of AS mice compared to control groups, and TSG treatment shifts the metabolic profiles of AS mice towards a normal state. At the transcriptional level, TSG significantly restores the expression of fatty acid metabolism-related genes (Srepb-1c, Fasn, Scd1, Gpat1, Dgat1, Pparα and Cpt1α), and regulates the expression levels of disturbed cholesterol metabolism-related genes (Srebp2, Hmgcr, Ldlr, Acat1, Acat2 and Cyp7a1) associated with lipid metabolism. Furthermore, at the cellular level, TSG remarkably polarizes aortic macrophages to their M2 phenotype. Our data demonstrate that TSG alleviates arthrosclerosis by dual-targeting to hepatic lipid metabolism and aortic M2 macrophage polarization in ApoE-/- mice, with significant implications for translational medicine and the treatment of AS using natural products.

Unexpected response of terrestrial carbon sink to rural depopulation in China.

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold. The results revealed that the proportion of the rural population in China decreased from 63.91 % in 2000 to 36.11 % in 2020. Human pressure decreased by 1.82% in rural depopulation areas, which promoted vegetation restoration in rural areas (+8.45 %) and increased the carbon sink capacity. The net primary productivity (NPP) and net ecosystem productivity (NEP) of the vegetation in the rural areas increased at rates of 2.95 g C m-2 yr-1 and 2.44 g C m-2 yr-1. Strong rural depopulation enhanced the carbon sequestration potential, and the NEP was 1.5 times higher in areas with sharp rural depopulation than in areas with mild rural depopulation. In addition, the rural depopulation was accompanied by urban expansion, and there was a positive correlation between the comprehensive urbanization level (CUL) and NEP in 75.29 % of urban areas. In the urban areas, the vegetation index increased by 88.42 %, and the urban green space partially compensated for the loss of carbon sink caused by urban expansion, with a growth rate of 4.96 g C m-2 yr-1. Changes in rural population have a nonlinear impact on the NEP. When the rural population exceeds 545.686 people/km2, an increase in the rural population will have a positive impact on the NEP. Our research shows that rural depopulation offers a potential opportunity to restore natural ecosystems and thus increase the carbon sequestration capacity.

Research progress on the relationship between phenotype and signaling pathways of pulmonary macrophages and asthma.

OBJECTIVE: The purpose of this study is to systematically investigate the different phenotypes and functional analyses of macrophages in lung tissue. DATA SOURCES: A search was performed using three databases (Web of Science, Science Direct, and MEDLINE) for all relevant studies published from January 1, 2019, to December 31, 2023. STUDY SELECTIONS: This systematic review complied with the PRlSMA document's requirements, including studies related to the signaling pathway relationship between pulmonary macrophages and asthma phenotype. The search includedstudies published in English or French lanquage, and was based on title, abstract, and complete textDocuments not meeting inclusion requirements were excluded. RESULTS: We have identified studies published within the past five years that meet the criteria for inclusion in this review. We found that asthma is a heterogeneous chronic inflammatory lung disease, and lung tissue macrophages are important immune cells in the respiratory tract. Pulmonary macrophages are also heterogeneous, as they have different subgroups with varying effector functions depending on the environment. They have different phenotypes and biological functions in different disease environments. The phenotypic changes of pulmonary macrophages occur during asthma, and the study of the different phenotypes and functions of macrophages in lung tissue is of great significance for treatment. CONCLUSIONS: This review summarizes current literature and provides a detailed introduction to the role of macrophages as key inflammatory mediators in the pathogenesis of asthma, as well as existing knowledge gaps. In addition, we propose that regulatory macrophages may prevent the development of asthma by producing IL-10, and regulating the polarization of pulmonary macrophages may be a new direction for asthma treatment.

Acute hepatotoxicity of intravenous amiodarone in a Becker muscular dystrophy patient with decompensated heart failing and ABCB4 gene mutation: as assessed for causality using the updated RUCAM.

BACKGROUND: Cardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation. CASE PRESENTATION: We present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient's liver function and clinical status rehabilitated. CONCLUSIONS: ABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.

LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-ß signalling pathway.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. METHODS: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. RESULTS: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFßR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFßR1 induced similar effects to H19 deficiency. CONCLUSIONS: In summary, our findings demonstrate that the H19/let-7 g/TGFßR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality in critical patients with diabetic ketoacidosis: a retrospective analysis of the eICU database.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis. Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death. Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023). Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency.