Longitudinal cohort study highlights cancer-preventive benefits of lipid-lowering drugs.

Cancer prevention is a serious global challenge. We aimed to investigate the relationship between lipid-lowering drugs and cancers. We included participants based on the UK Biobank. Lipid-lowering drug use was defined as new users before enrollment and the primary outcome was cancer incidence. The Cox proportional hazards regression model was used to evaluate the association between drug use and outcome. We also performed a meta-analysis. We found that lipid-lowering drugs were associated with decreased risk of 21 types of cancers, including melanoma, skin cancer, and reproductive, hematological, urinary, digestive, nervous, and endocrine system cancers (all p < 0.0010). Our meta-analysis documented that lipid-lowering drugs reduced the risk of prostate, liver, and gastric cancers, especially (all p < 0.050). Overall, lipid-lowering drugs had protective associations with cancer incidence, suggesting the possible cancer prevention effects even in the general population.

High-Dose Furmonertinib in Patients With EGFR-Mutated NSCLC and Leptomeningeal Metastases: A Prospective Real-World Study.

INTRODUCTION: Leptomeningeal metastasis (LM) is one of the most severe complications of NSCLC. Furmonertinib is a pan-EGFR tyrosine kinase inhibitor (TKI) with a high rate of brain penetration and a wide therapeutic window. Here, we evaluated the efficacy and safety of high-dose furmonertinib in patients with EGFR-mutated NSCLC and LM. METHODS: This prospective real-world study included patients with EGFR-mutated NSCLC and LM treated with a high-dose furmonertinib (240 mg once daily) as a monotherapy or in combination with other treatments. The primary end point was overall survival, and the secondary end points included time to treatment discontinuation and clinical response rate. Additional efficacy evaluations included changes in brain magnetic resonance imaging by the response assessment in neuro-oncology-LM radiologic criteria. We also introduced next-generation sequencing-based assays to evaluate genomic and epigenomic features of cell-free DNA (cfDNA) in patients' cerebrospinal fluid (CSF) samples and to analyze their associations with patient outcomes. RESULTS: We enrolled 48 patients, of whom 35 (72.9%) had received third-generation EGFR TKIs. The median overall survival was 8.43 months (95% confidence interval: 5.48-11.39 mo), while the median time to treatment discontinuation was 8.27 months (95% confidence interval: 5.40-11.14 mo), and the clinical response rate was 75%. The LM objective response rate and disease control rate assessed with response assessment in neuro-oncology-LM radiologic criteria were 50.0% and 92.1%, respectively. The adverse event profiles were consistent with previous reports of furmonertinib. Briefly, 22 (45.8%) had adverse events possibly related to furmonertinib and 3 (6.3%) had a grade 3-elevated aminotransaminase or nausea or leucopenia, leading to a dose reduction to 160 mg daily. Furthermore, methylation analysis of cfDNA in CSF revealed that there was a considerable correlation between the changes of aberrant methylated fragments from lung cancer cells and the response of the patients. Meanwhile, the copy number burden scores derived from the low-pass whole genome sequencing assay may offer another objective and effective method for the diagnosis and evaluation of treatment efficacy in LM. CONCLUSIONS: In the real world, the high-dose furmonertinib-based treatment may potentially have clinical efficacy and tolerable safety in patients of EGFR-mutated NSCLC with LM, even in patients previously treated with other third-generation EGFR TKIs. Methylation and copy number burden analysis of cfDNA in CSF may be considered objective indicators for the diagnosis of LM and evaluation of treatment response.

Eriodictyol attenuates osteoarthritis progression through inhibiting inflammation via the PI3K/AKT/NF-κB signaling pathway.

Eriodictyol, a flavonoid distributed in citrus fruits, has been known to exhibit anti-inflammatory activity. In this study, destabilized medial meniscus (DMM)-induced OA model was used to investigate the protective role of eriodictyol on OA. Meanwhile, we used an IL-1ß-stimulated human osteoarthritis chondrocytes model to investigate the anti-inflammatory mechanism of eriodictyol on OA. The production of nitric oxide was detected by Griess reaction. The productions of MMP1, MMP3, and PGE2 were detected by ELISA. The expression of LXRα, ABCA1, PI3K, AKT, and NF-κB were measured by western blot analysis. The results demonstrated that eriodictyol could alleviate DMM-induced OA in mice. In vitro, eriodictyol inhibited IL-1ß-induced NO, PGE2, MMP1, and MMP3 production in human osteoarthritis chondrocytes. Eriodictyol also suppressed the phosphorylation of PI3K, AKT, NF-κB p65, and IκBα induced by IL-1ß. Meanwhile, eriodictyol significantly increased the expression of LXRα and ABCA1. Furthermore, eriodictyol disrupted lipid rafts formation through reducing the cholesterol content. And cholesterol replenishment experiment showed that adding water-soluble cholesterol could reverse the anti-inflammatory effect of eriodictyol. In conclusion, the results indicated eriodictyol inhibited IL-1ß-induced inflammation in human osteoarthritis chondrocytes through suppressing lipid rafts formation, which subsequently inhibiting PI3K/AKT/NF-κB signaling pathway.

Thoracoscopic pulmonary resection combined with real-time image-guided percutaneous ablation for multiple pulmonary nodules: a novel surgical approach and literature review.

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

Precisely targeted drug delivery by mesenchymal stem cells-based biomimetic liposomes to cerebral ischemia-reperfusion injured hemisphere.

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.

CD63 + tumor-associated macrophages drive the progression of hepatocellular carcinoma through the induction of epithelial-mesenchymal transition and lipid reprogramming.

BACKGROUND: Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Activated platelet-derived exosomal LRG1 promotes multiple myeloma cell growth.

The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.

Coupling Process between Droplet and Iron Investigated by Reactive Molecular Dynamics Simulations.

The droplet-to-iron electrochemical reaction is common in nature and industrial production, and it causes damage to the economy, safety, and the environment. The electrochemical reaction of droplet-to-iron is a coupling process of wetting and corrosion. Presently, investigations into electrochemical reactions mainly focus on the corrosions caused by a solution, and wetting is rarely considered. However, for the droplet-to-iron electrochemical reaction, the mechanism of charge transfer in the process is still unclear. In this paper, a reactive molecular dynamics simulation model for the droplet-to-iron electrochemical reaction is developed for the first time. The electrochemical reaction of droplet-to-iron is studied, and the interaction between droplet wetting and corrosion on iron is investigated. The effects of temperature, electric field strength, and salt concentration on the electrochemical reaction are explored. Results show that droplet wetting on the iron surface and the formation of a single-molecular-layer ordered structure are prerequisites for corrosion. The hydroxyl radicals that penetrate the ordered structure acquire electrons from iron atoms on the substrate surface under the action of Coulomb forces and form iron-containing oxides with these iron atoms. The corrosion products and craters lead to a reduced droplet height, which promotes droplet wetting on iron and further intensifies the droplet-to-iron electrochemical reaction.

Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization.

BACKGROUND: Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear. METHOD: In this study, we utilized summary-level data from genome-wide association studies (GWAS) focused on appendicular lean mass (ALM), hand grip strength, and walking pace. Single nucleotide polymorphisms (SNPs) were employed as genetic instruments for IL-6 and IL-6R to estimate the causal effect of sarcopenia traits. We adopted the Mendelian randomization (MR) approach to investigate these associations using the inverse variance weighted (IVW) method as the primary analytical approach. Additionally, we performed sensitivity analyses to validate the reliability of the MR results. RESULT: This study revealed a significant negative association between main IL-6R and eQTL IL-6R on the left grip strength were - 0.013 (SE = 0.004, p < 0.001) and -0.029 (SE = 0.007, p < 0.001), respectively. While for the right grip strength, the estimates were - 0.011 (SE = 0.001, p < 0.001) and - 0.021 (SE = 0.008, p = 0.005). However, no evidence of an association for IL-6R with ALM and walking pace. In addition, IL-6 did not affect sarcopenia traits. CONCLUSION: Our study findings suggest a negative association between IL-6R and hand grip strength. Additionally, targeting IL-6R may hold potential value as a therapeutic approach for the treatment of hand grip-related issues.

Study on microstructure evolution of waxy crude oil emulsions under dynamic cooling conditions.

A rheo-microscopy in situ synchronous measurement system was utilized to investigate the dynamic behavior of water droplets in W/O waxy crude oil emulsions subjected to dynamic cooling conditions, the microstructural evolution of water droplets aggregates can be categorized into three stages based on the various forms of wax crystals. The results show that under the joint action of wax crystals and water droplets, the water droplets aggregation trend and complexity in the system are negatively correlated with the changes of temperature and shear rate, and the water droplets movement behavior is positively correlated with the changes of temperature and shear rate. As the temperature decreases, the minimum edge distance of water droplets decreases by a maximum of 32.1%, the specific surface area (SA) decreases by a maximum of 12.0%, and the fractal dimension increases by a maximum of 11.7%. As the shear rate increases, the minimum edge distance of water droplets increases by up to 27.9%, the specific surface area (SA) increases by up to 10.1%, and the fractal dimension decreases by up to 8.5%. Additionally, an analysis is conducted on the collision aggregation behavior of water droplets in shear flow field based on population balance theory.

Preparation and Characterization of Pullulan-Based Packaging Paper for Fruit Preservation.

Improving the shelf lives of fruits is challenging. The biodegradable polysaccharide pullulan exhibits excellent film-forming ability, gas barrier performance, and natural decomposability, making it an optimal material for fruit preservation. To overcome problems of high cost and film porosity of existing packaging technologies, we aimed to develop pullulan-based packaging paper to enhance the shelf lives of fruits. A thin paper coating comprising a mixture of 15 wt.% pullulan solution at various standard viscosities (75.6, 77.8, and 108.5 mPa·s) with tea polyphenols (15:2) and/or vitamin C (150:1) improved the oxygen transmission rate (120-160 cm3 m-2·24 h·0.1 MPa), water vapor transmission rate (<5.44 g·mm-1 m-2·h·kPa), maximum free radical clearance rate (>87%), and antibacterial properties of base packaging paper. Grapes wrapped with these pullulan-based papers exhibited less weight loss (>4.41%) and improved hardness (>16.4%) after 10 days of storage compared to those of control grapes (wrapped in untreated/base paper). Grapes wrapped with pullulan-based paper had >12.6 wt.% total soluble solids, >1.5 mg/g soluble protein, >0.44 wt.% titratable acidity, and ≥4.5 mg 100 g-1 ascorbic acid. Thus, pullulan-based paper may prolong the shelf life of grapes with operational convenience, offering immense value for fruit preservation.

Association Between Nitrogen Dioxide Pollution and Cause-Specific Mortality in China: Cross-Sectional Time Series Study.

BACKGROUND: Nitrogen dioxide (NO2) has been frequently linked to a range of diseases and associated with high rates of mortality and morbidity worldwide. However, there is limited evidence regarding the risk of NO2 on a spectrum of causes of mortality. Moreover, adjustment for potential confounders in NO2 analysis has been insufficient, and the spatial resolution of exposure assessment has been limited. OBJECTIVE: This study aimed to quantitatively assess the relationship between short-term NO2 exposure and death from a range of causes by adjusting for potential confounders in Guangzhou, China, and determine the modifying effect of gender and age. METHODS: A time series study was conducted on 413,703 deaths that occurred in Guangzhou during the period of 2010 to 2018. The causes of death were classified into 10 categories and 26 subcategories. We utilized a generalized additive model with quasi-Poisson regression analysis using a natural cubic splines function with lag structure of 0 to 4 days to estimate the potential lag effect of NO2 on cause-specific mortality. We estimated the percentage change in cause-specific mortality rates per 10 µg/m3 increase in NO2 levels. We stratified meteorological factors such as temperature, humidity, wind speed, and air pressure into high and low levels with the median as the critical value and analyzed the effects of NO2 on various death-causing diseases at those high and low levels. To further identify potentially vulnerable subpopulations, we analyzed groups stratified by gender and age. RESULTS: A significant association existed between NO2 exposure and deaths from multiple causes. Each 10 µg/m3 increment in NO2 density at a lag of 0 to 4 days increased the risks of all-cause mortality by 1.73% (95% CI 1.36%-2.09%) and mortality due to nonaccidental causes, cardiovascular disease, respiratory disease, endocrine disease, and neoplasms by 1.75% (95% CI 1.38%-2.12%), 2.06% (95% CI 1.54%-2.59%), 2.32% (95% CI 1.51%-3.13%), 2.40% (95% CI 0.84%-3.98%), and 1.18% (95% CI 0.59%-1.78%), respectively. Among the 26 subcategories, mortality risk was associated with 16, including intentional self-harm, hypertensive disease, and ischemic stroke disease. Relatively higher effect estimates of NO2 on mortality existed for low levels of temperature, relative humidity, wind speed, and air pressure than with high levels, except a relatively higher effect estimate was present for endocrine disease at a high air pressure level. Most of the differences between subgroups were not statistically significant. The effect estimates for NO2 were similar by gender. There were significant differences between the age groups for mortality due to all causes, nonaccidental causes, and cardiovascular disease. CONCLUSIONS: Short-term NO2 exposure may increase the risk of mortality due to a spectrum of causes, especially in potentially vulnerable populations. These findings may be important for predicting and modifying guidelines for NO2 exposure in China.

Role of interleukin­32 in cancer progression (Review).

Interleukin (IL)-32 is induced by pro-inflammatory cytokines and promotes the release of inflammatory cytokines. Therefore, it can promote inflammatory responses. The present review article summarized the role of the receptors required for IL-32 action, the biological function of IL-32 and its mechanism of action in tumors. Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.

Investigating the relationship between muscle mass and nasal Methicillin-Resistant Staphylococcus aureus (MRSA) colonization: Analysis of the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is associated with an increased risk of infection disease. Low muscle mass has been linked to higher levels of inflammatory markers and weakened immune response, which may impact the susceptibility to nasal MRSA colonization. The relationship between muscle function and immune response to pathogens may be bidirectional. This study investigates the association between muscle mass and nasal MRSA colonization in adults. METHODS: The present cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Appendicular skeletal muscle mass (ASM) adjusted by body mass index (BMI) (ASM/BMI) was used to evaluate muscle mass. Multivariate logistic regression, adjusted for demographic and infection factors, was used to analyze the association between muscle mass and nasal colonization by MRSA. A subgroup analysis based on age and gender was performed to assess the impact of muscle mass on nasal MRSA colonization. RESULTS: Nasal MRSA colonization was more prevalent in females, those with smaller household sizes, lower income, lower ASM/BMI, those who had stayed in healthcare facilities in the past 12 months, and individuals with diabetes and smoking habits. After adjusting for confounding factors, a dose-dependent association was found between decreasing quartiles of ASM/BMI and the risk of nasal MRSA colonization (p < 0.05). Additionally, per 1 unit increase in ASM/BMI was related to a 64% lower risk of nasal MRSA colonization. CONCLUSIONS: This study suggests a significant negative correlation between ASM/BMI and the risk of nasal MRSA colonization. However, more prospective studies are required to investigate the causal relationship between muscle mass and colonization.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets.

BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. METHODS: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. RESULTS: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048- 1.357). On the other hand, CFHR1 (0.621, 0.497-0.776) and CFHR2 (0.824, 0.703-0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707-0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036-1.314). Additionally, C1S (0.111, 0.018-0.672), C7 (1.631, 1.190-2.236), and CFHR2 (1.279, 1.059-1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. CONCLUSION: Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

The classification of obesity based on metabolic status redefines the readmission of non-Hodgkin's lymphoma-an observational study.

BACKGROUND: The relationship between obesity and non-Hodgkin's lymphoma (NHL) was controversial, which may be due to the crudeness definition of obesity based on body mass index (BMI). As obesity and metabolic abnormalities often coexist, we aimed to explore whether the classification of obesity based on metabolic status can help to evaluate the real impact of obesity on the readmission of NHL. METHODS: In this retrospective cohort study, utilizing the 2018 Nationwide Readmissions Database, we identified NHL-related index hospitalizations and followed them for non-elective readmission. The patients with NHL were classified as metabolically healthy non-obese (MHNO) and obese (MHO) and metabolically unhealthy non-obese (MUNO) and obese (MUO). Readmission rates for each phenotype were calculated at 30-day intervals. Multiple COX regression was used to analyze the association of metabolic-defined obesity with 30-day, 90-day, and 180-day readmission rates in patients with NHL. RESULTS: There were 22,086 index hospitalizations with NHL included. In the multivariate COX regression, MUNO was associated with increased 30-day (HR = 1.113, 95% CI 1.036-1.195), 90-day (HR = 1.148, 95% CI 1.087-1.213), and 180-day readmission rates (HR = 1.132, 95% CI 1.077-1.189), and MUO was associated with increased 30-day (HR=1.219, 95% CI: 1.081-1.374), 90-day (HR = 1.228, 95% CI 1.118-1.348), and 180-day readmission rates (HR = 1.223, 95% CI 1.124-1.33), while MHO had no associations with readmission rates. CONCLUSIONS: The presence of metabolic abnormalities with or without obesity increased the risk of non-selective readmission in patients with NHL. However, obesity alone had no associations with the risk of non-selective readmission, suggesting that interventions for metabolic abnormalities may be more important in reducing readmissions of NHL patients.

Mortality Risk and Burden From a Spectrum of Causes in Relation to Size-Fractionated Particulate Matters: Time Series Analysis.

BACKGROUND: There is limited evidence regarding the adverse impact of particulate matters (PMs) on multiple body systems from both epidemiological and mechanistic studies. The association between size-fractionated PMs and mortality risk, as well as the burden of a whole spectrum of causes of death, remains poorly characterized. OBJECTIVE: We aimed to examine the wide range of susceptible diseases affected by different sizes of PMs. We also assessed the association between PMs with an aerodynamic diameter less than 1 µm (PM1), 2.5 µm (PM2.5), and 10 µm (PM10) and deaths from 36 causes in Guangzhou, China. METHODS: Daily data were obtained on cause-specific mortality, PMs, and meteorology from 2014 to 2016. A time-stratified case-crossover approach was applied to estimate the risk and burden of cause-specific mortality attributable to PMs after adjusting for potential confounding variables, such as long-term trend and seasonality, relative humidity, temperature, air pressure, and public holidays. Stratification analyses were further conducted to explore the potential modification effects of season and demographic characteristics (eg, gender and age). We also assessed the reduction in mortality achieved by meeting the new air quality guidelines set by the World Health Organization (WHO). RESULTS: Positive and monotonic associations were generally observed between PMs and mortality. For every 10 µg/m3 increase in 4-day moving average concentrations of PM1, PM2.5, and PM10, the risk of all-cause mortality increased by 2.00% (95% CI 1.08%-2.92%), 1.54% (95% CI 0.93%-2.16%), and 1.38% (95% CI 0.95%-1.82%), respectively. Significant effects of size-fractionated PMs were observed for deaths attributed to nonaccidental causes, cardiovascular disease, respiratory disease, neoplasms, chronic rheumatic heart diseases, hypertensive diseases, cerebrovascular diseases, stroke, influenza, and pneumonia. If daily concentrations of PM1, PM2.5, and PM10 reached the WHO target levels of 10, 15, and 45 µg/m3, 7921 (95% empirical CI [eCI] 4454-11,206), 8303 (95% eCI 5063-11,248), and 8326 (95% eCI 5980-10690) deaths could be prevented, respectively. The effect estimates of PMs were relatively higher during hot months, among female individuals, and among those aged 85 years and older, although the differences between subgroups were not statistically significant. CONCLUSIONS: We observed positive and monotonical exposure-response curves between PMs and deaths from several diseases. The effect of PM1 was stronger on mortality than that of PM2.5 and PM10. A substantial number of premature deaths could be preventable by adhering to the WHO's new guidelines for PMs. Our findings highlight the importance of a size-based strategy in controlling PMs and managing their health impact.

Acute Basophilic Leukemia Arising from Chronic Myeloid Leukemia with +8, I(17q)(q10) and der(22)t(9;22) After Imatinib Therapy.

Acute basophilic leukemia (ABL) arising from chronic myeloid leukemia (CML) with abundant mast cells (MCs), coexisting with a complex karyotype is rare. Here, we report an 81-year-old man admitted to our hospital with a history of ABL. He was diagnosed with CML in the chronic phase in January 2018, and Imatinib was used at a daily dose of 400mg. Then, transformation to ABL with abundant MCs in the bone marrow and complex karyotypes including 48,XY, trisomy 8 (+8), isochromosome 17(q10) [i(17)(q10)], and derivative chromosome 22 t(9;22) [der(22)t(9;22)] were discovered simultaneously in January 2022. In conclusion, the increased number of MCs in our case is a reminder that they might play an important role in the prognosis of CML and trigger the development of complex karyotypes. Moreover, this is the first case report of ABL arising from CML with abundant MCs, coexisting with 48,XY, +8, i(17)(q10), and der(22)t(9;22), during Imatinib treatment. Further studies are needed to better characterize this rare condition.