Associations between multiple urinary metals and metabolic syndrome: Exploring the mediating role of liver function in Chinese community-dwelling elderly.

BACKGROUND: Multiple metals exposure has been revealed to be related to metabolic syndrome (MetS). However, the associations and interactions between multiple metals exposure and MetS are remains controversial, and the potential mechanism of the above-mentioned is still unclear. METHODS: The associations between urinary metals and the MetS were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Bayesian kernel machine regression (BKMR) model and quantile-based g-computation (qgcomp) were applied to explore the mixed exposure and interaction effect of metals. Mediation analysis was used to explore the role of liver function. RESULTS: In the single metal model, multiple metals were significantly associated with MetS. RCS analysis further verified the associations between 8 metals and MetS. BKMR model and qgcomp showed that zinc (Zn), iron (Fe), and tellurium (Te) were the main factors affecting the overall effect. In addition, mediation analysis indicated that serum alanine aminotransferase (ALT) mediated 21.54% and 13.29% in the associations of vanadium (V) and Zn with the risk of MetS, respectively. CONCLUSIONS: Elevated urinary concentration of Zn, V, Te, copper (Cu), molybdenum (Mo), and thallium (Tl) were related to the increased risk of MetS. Conversely, Fe and selenium (Se) may be protective factors for MetS in mixed exposure. Liver function may play a key role in the association of V and Zn exposure with MetS.

Non-pharmaceutical interventions for depressive symptoms in patients with breast cancer: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Patients with breast cancer often suffer from depressive symptoms throughout various stages of cancer, significantly impacting their quality of life and treatment outcomes. Non-pharmaceutical interventions such as psychotherapy, mind-body therapies and physical exercise have shown effectiveness in addressing cancer-related depression. However, the efficacy and safety of different non-pharmacological interventions remain a topic of debate. Therefore, to provide an objective assessment and comparison of the impact of different non-pharmaceutical interventions on depression, we will conduct a network meta-analysis (NMA) to explore the effects of different non-pharmaceutical interventions on reducing depressive symptoms among patients with breast cancer. METHODS AND ANALYSIS: We will search nine Chinese and English-language databases, from database inception to 31 July 2023, for randomised controlled trials published in Chinese or English. The English-language databases are PubMed, Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials, and the Chinese databases are CBM, CNKI, VIP and Wanfang. Two independent researchers will perform information extraction from eligible articles. The primary outcome will be the changes in depressive symptoms, while the secondary outcome will include adverse events. STATA V.15.0 will be used to conduct paired meta-analysis and NMA. Grading of Recommendations Assessment, Development and Evaluation will be used to assess the quality of evidence, and the Cochrane tool for assessing the risks of bias in randomised trials V.2 will be used for risk of bias assessment. ETHICS AND DISSEMINATION: The study does not require ethical approval as it will analyse data from existing studies. It is expected that the results of the study will be published in peer-reviewed journals and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42023450494.

High Performance Indium-Tin-Oxide Schottky Diodes for Terahertz Band Operation.

Schottky diode, capable of ultrahigh frequency operation, plays a critical role in modern communication systems. To develop cost-effective and widely applicable high-speed diodes, researchers have delved into thin-film semiconductors. However, a performance gap persists between thin-film diodes and conventional bulk semiconductor-based ones. Featuring high mobility and low permittivity, indium-tin-oxide has emerged to bridge this gap. Nevertheless, due to its high carrier concentration, indium-tin-oxide has predominantly been utilized as electrode rather than semiconductor. In this study, a remarkable quantum confinement induced dedoping phenomenon was discovered during the aggressive indium-tin-oxide thickness downscaling. By leveraging such a feature to change indium-tin-oxide from metal-like into semiconductor-like, in conjunction with a novel heterogeneous lateral design facilitated by an innovative digital etch, we demonstrated an indium-tin-oxide Schottky diode with a cutoff frequency reaching terahertz band. By pushing the boundaries of thin-film Schottky diodes, our research offers a potential enabler for future fifth-generation/sixth-generation networks, empowering diverse applications.

The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Vancomycin trough concentration in adult patients with periprosthetic joint infection: A machine learning-based covariate model.

AIMS: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients. METHODS: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP). RESULTS: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R2 =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set. CONCLUSION: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment.

Electronic symptom monitoring for home-based palliative care: A systematic review.

BACKGROUND: Coordination and communication challenges in home-based palliative care complicate transitions from hospital care. Electronic symptom monitoring enables real-time data collection, enhancing patient-provider communication. However, a systematic evaluation of its effectiveness in home-based palliative care is lacking. AIM: To analyze the feasibility, effectiveness, and limitations of electronic symptom monitoring in home-based palliative care, assess the evidence quality, identify the evidence gap, and suggest implications for future research and practice. DESIGN: This study uses systematic review, meta-analysis, and narrative synthesis (CRD42023457977) to analyze relevant studies until September 2023. DATA SOURCES: Electronic searches in MEDLINE, CENTRAL, and Embase until September 2023, complemented by hand-searching of references and citations. RESULTS: This study included twenty studies. The majority of patients positively engage in electronic symptom monitoring, which could improve their quality of life, physical and emotional well-being, and symptom scores without a significant increase in costs. However, firm conclusions about the effects of electronic symptom monitoring on outcomes like survival, hospital admissions, length of stay, emergency visits, and adverse events were limited due to significant variability in the reported data or inadequate statistical power. CONCLUSION: Introducing electronic symptom monitoring in home-based palliative care holds potential for enhancing patient-reported outcomes, potentially decreasing hospital visits and costs. However, inconsistency in current studies arising from diverse monitoring systems obstructs comparability. To advance, future high-quality research should employ standardized follow-up periods and established scales to better grasp the benefits of electronic symptom monitoring in home-based palliative care.

177Lu-FAP-2286 Therapy in a Patient With Metastatic Rhabdoid Meningioma.

ABSTRACT: Rhabdoid meningioma is a rare subtype of meningioma and has a poor prognosis. Herein, we reported a patient of rhabdoid meningioma with multiple liver, pancreas, and bone metastases, who received 177Lu-FAP-2286 therapy. After 1 treatment cycle, 68Ga-FAP-2286 PET/CT revealed partial remission of the lesions.

The quality of life impacting factors in malnourished patients with gastric cancer.

Introduction: Malnutrition is prevalent among individuals with gastric cancer and notably decreases their quality of life (QOL). However, the factors impacting QOL are yet to be clearly defined. This study aimed to identify essential factors impacting QOL in malnourished patients suffering from gastric cancer. Methods: By using the Patient-Generated Subjective Global Assessment (PG-SGA) to assess the nutritional status (≥4 defined malnutrition) of hospitalized cancer patients, 4,586 gastric cancer patients were ultimately defined as malnourished. Spearman method was used to calculate the relationship between clinical features and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Then, univariate and multivariate logistic regression were used to observe which factors affected QOL, and subgroup analysis was performed in young and old population respectively. In addition, we used univariate and multivariate logistic regression to explore whether and how self-reported frequent symptoms in the last 2 weeks of the PG-SGA score affected QOL. Results: In multivariate logistic regression analysis of clinical features of patients with malnourished gastric cancer, women, stage II, stage IV, WL had an independent correlation with a low global QOL scores. However, BMI, secondary education, higher education, surgery, chemotherapy, HGS had an independent correlation with a high global QOL scores. In multivariate logistic regression analysis of symptoms in self-reported PG-SGA scores in patients with malnourished gastric cancer, having no problem eating had an independent correlation with a high global QOL scores. However, they have no appetite, nausea, vomiting, constipation and pain had an independent correlation with a lower global QOL scores. The p values of the above statistical results are both < 0.05. Conclusion: This study demonstrates that QOL in malnourished patients with gastric cancer is determined by female sex, stage II, stage IV, BMI, secondary and higher education or above, surgery, chemotherapy, WL, and HGS. Patients' self-reported symptoms of nearly 2 weeks, obtained by using PG-SGA, are also further predictive of malnourished gastric cancer patients. Detecting preliminary indicators of low QOL could aid in identifying patients who might benefit from an early referral to palliative care and assisted nursing.

Correlations of dynamic changes in lipid and protein of salted large yellow croaker during storage.

Protein and lipid are two major components that undergo significant changes during processing of aquatic products. This study focused on the protein oxidation, protein conformational states, lipid oxidation and lipid molecule profiling of salted large yellow croaker during storage, and their correlations were investigated. The degree of oxidation of protein and lipid was time-dependent, leading to an increase in carbonyl content and surface hydrophobicity, a decrease in sulfhydryl groups, and an increase in conjugated diene, peroxide value and thiobarbituric acid reactive substances value. Oxidation caused protein structure denaturation and aggregation during storage. Lipid composition and content changed dynamically, with polyunsaturated phosphatidylcholine (PC) was preferentially oxidized compared to polyunsaturated triacylglycerol. Correlation analysis showed that the degradation of polyunsaturated key differential lipids (PC 18:2_20:5, PC 16:0_22:6, PC 16:0_20:5, etc.) was closely related to the oxidation of protein and lipid. The changes in protein conformation and the peroxidation of polyunsaturated lipids mutually promote each other's oxidation process.

Identification of Potential Biomarkers for Major Depressive Disorder: Based on Integrated Bioinformatics and Clinical Validation.

Major depressive disorder (MDD) is a severe mental illness characterized by a lack of objective biomarkers. Mounting evidence suggests there are extensive transcriptional molecular changes in the prefrontal cortex (PFC) of individuals with MDD. However, it remains unclear whether there are specific genes that are consistently altered and possess diagnostic power. In this study, we conducted a systematic search of PFC datasets of MDD patients from the Gene Expression Omnibus database. We calculated the differential expression of genes (DEGs) and identified robust DEGs using the RRA and MetaDE methods. Furthermore, we validated the consistently altered genes and assessed their diagnostic power through enzyme-linked immunosorbent assay experiments in our clinical blood cohort. Additionally, we evaluated the diagnostic power of hub DEGs in independent public blood datasets. We obtained eight PFC datasets, comprising 158 MDD patients and 263 healthy controls, and identified a total of 1468 unique DEGs. Through integrated analysis, we identified 290 robustly altered DEGs. Among these, seven hub DEGs (SLC1A3, PON2, AQP1, EFEMP1, GJA1, CENPD, HSD11B1) were significantly down-regulated at the protein level in our clinical blood cohort. Moreover, these hub DEGs exhibited a negative correlation with the Hamilton Depression Scale score (P < 0.05). Furthermore, these hub DEGs formed a panel with promising diagnostic power in three independent public blood datasets (average AUCs of 0.85) and our clinical blood cohort (AUC of 0.92). The biomarker panel composed of these genes demonstrated promising diagnostic efficacy for MDD and serves as a useful tool for its diagnosis.

Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.

Successful Treatment of Cutaneous Protothecosis Due to Prototheca wickerhamii with Terbinafine.

Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid-Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.

No genetic causal association between periodontitis and ankylosing spondylitis: a bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Observational studies that reveal an association between periodontitis (PD) and ankylosing spondylitis (AS) exist. However, observational research is prone to reverse causality and confounding factors, which make it challenging to infer cause-and-effect relationships. We conducted a two-sample Mendelian randomization (MR) study to examine the causal relationship between the genetic prediction of PD and AS. METHODS: In our study, single-nucleotide polymorphisms (SNPs) were defined as instrumental variables (IVs). The genetic association with PD came from the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) consortium, wherein 17353 cases of European ancestry and 28210 controls of European ancestry were included in this study. The genetic association with AS from the Neale Laboratory Consortium included 337,159 individuals from the United Kingdom, with 968 cases and 336,191 controls. MR analysis was mainly performed using the inverse-variance weighted (IVW) method. In addition, the robustness of the study findings was assessed using sensitivity, pleiotropy, and heterogeneity analyses. RESULTS: Eighteen independent SNPs with P-values significantly smaller than 1 × 10- 5 were used as IV SNPs for PD, while 39 independent SNPs with P-values significantly smaller than 1 × 10- 5 were used as IV SNPs for AS. The results of the IVW method revealed no causal association between PD and AS (odds ratio = 1.00, 95% confidence interval: 0.99953 to 1.00067, P = 0.72). The MR-Egger method did not support the causal association between PD and AS. It is unlikely that horizontal pleiotropy distorts causal estimates based on sensitivity analysis. No significant heterogeneity was observed in the Q test. The ''leave-one-out'' analysis demonstrated that the robustness of our results was unaffected by eliminating any of the IVs. Likewise, no significant causative effect for AS on PD was observed in the inverse MR analysis. CONCLUSIONS: The study results do not support shared heritability or a causal association between PD and AS.

Landscape of Nuclear Medicine in China and Its Progress on Theranostics.

Nuclear medicine in China started in 1956 and, with the rapid development of the economy and continuous breakthroughs in precision medicine, has made significant progress in recent years. Almost 13,000 staff members in nearly 1,200 hospitals serve more than 3.9 million patients each year. Over the past decade, the radiopharmaceutical industry has developed rapidly, with the initial formation of a complete industrial chain of production of various radiopharmaceuticals for both clinical use and basic research. Advanced equipment such as PET/CT scanners is being manufactured domestically and even installed abroad. Recently, research into screening and synthesizing new target probes and their translation into the clinic has gained more attention, with various new tracers with potential clinical value being thoroughly studied. Simultaneously, 68Ga- and 177Lu-labeled tumor-targeted probes and others have been implemented for theranostics in an increasing number of hospitals and would be helped by approval from the National Medical Products Administration. Over the next 10-20 y, with the launch of the Mid- and Long-Term Development Plan for Medical Isotopes (2021-2035) by the Chinese government, there is great potential for nuclear medicine in China. With the rise in independent innovation in manufacturing, the shortage of radiopharmaceuticals will be effectively curtailed. We anticipate that the scale of nuclear medicine will at least double by 2035, covering all high-grade hospitals and leading to the aim of "one county, one department" in China.

Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis.

This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib, a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer (ES-SCLC). This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC. Population pharmacokinetic (PopPK) and exposure-response (E-R) analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC. PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17% higher than that in non-Chinese patients with ES-SCLC. Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact. E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m2, without notable changes in myeloprotective or antitumor efficacy. However, the incidence of infusion site reactions, headaches, and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC. These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients. They support the adoption of a 240-mg/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.

Physiochemical characterization and ameliorative effect of rice resistant starch modified by heat-stable α-amylase and glucoamylase on the gut microbial community in T2DM mice.

In the presented study, natural rice containing high resistant starch content was used as a raw material to produce rice resistant starch (RRS) through enzymatic hydrolysis with heat-stable α-amylase and glucoamylase. The chemical composition, structural characteristics and in vitro glycemic index (GI) of RRS were evaluated. The effects of RRS at different doses on the body weight, serum biochemical levels, pathological indexes, production of short-chain fatty acids (SCFAs) in the gut and the intestinal microbial composition in T2DM mice were investigated. The results of physiochemical characterization indicated that, relative to rice flour, RRS mainly comprising resistant starch had higher crystallinity (25.85%) and a more stable structure, which contributed to its lower digestibility and decreased GI in vitro. Compared with the model control group, 1 g per kg BW and 2 g per kg BW oral gavage dosages of RRS effectively enhanced the SCFA productivity in the T2DM mouse gut, as well as alleviating T2DM symptoms, involving an increase in body weight, reduction in fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine transaminase and aspartate aminotransferase, and an increase in serum insulin and high-density lipoprotein cholesterol. Besides, 1 g per kg BW and 2 g per kg BW dosages of RRS mitigated T2DM-induced pancreas damage. Furthermore, up-regulation in the abundance of probiotics (Lactobacillus, Ruminococcus, etc.) and down-regulation in the number of harmful bacteria (Desulfovibrio, Prevotella, etc.) were observed in all RRS-treated groups. In summary, this work suggested that RRS prepared using heat-stable α-amylase and glucoamylase could be a potential functional component for amelioration of T2DM applied in the fields of food and pharmaceutics.

Elevated remnant cholesterol is a risk factor for acute ischemic stroke.

OBJECTIVES: Remnant cholesterol (RC) is thought to be an important pathogenic risk factor for atherosclerosis, however, the relationship between RC and acute ischemic stroke (AIS) is still unclear. This study aimed to determine whether fasting blood RC level is an independent risk factor for AIS. MATERIALS AND METHODS: A retrospective analysis was performed on 650 patients with AIS and 598 healthy controls during the same time period. The association between RC and AIS was investigated using binary logistic regression, and the relationship between RC and AIS risk was demonstrated using Restricted Cubic Splines (RCS). RESULTS: RC was significantly higher in the AIS group compared with control group, and was an independent risk factor for AIS when the covariates were not adjusted;After adjusting some covariates, RC was still an independent risk factor for AIS. The RCS analysis found the risk was non-linear: when RC concentration was less than 0.69 mol/L, the risk of AIS increased with the elevation of RC, and when RC concentration was more than or equal to 0.69 mol/L, the risk of AIS was insignificant with the elevation of RC. Correlation analysis revealed that RC was associated with diabetes and fasting glucose. Further analysis revealed that the incidence of AIS in diabetic patients increased significantly with the increase of RC, and RCS analysis revealed that the risk of AIS in diabetic patients increased with the increase of RC when RC was more than 1.15 mol/L. CONCLUSIONS: This study confirms RC as an independent risk factor for AIS, which highlights a distinct non-linear association between RC levels and AIS risk. These findings suggest the need for targeted AIS risk assessment strategies, especially in diabetic patients, and underscore the relevance of RC as a biomarker in AIS risk stratification.

A retrospective study of 68Ga-FAPI PET/CT in differentiating the nature of pulmonary lesions.

Purpose: This study aimed to investigate the characteristics of various pulmonary lesions as revealed by 68Ga-FAPI PET/CT and to determine the utility of 68Ga-FAPI PET/CT in distinguishing the nature of these pulmonary lesions. Methods: A retrospective analysis was conducted on 99 patients with pulmonary lesions, who were categorized into three distinct groups: primary lung tumors (G1), metastatic lung tumors (G2), and benign lesions (G3). Each participant underwent a 68Ga-FAPI PET/CT scan. Among these groups, variables such as the Tumor/Background Ratio (TBR), Maximum Standardized Uptake Value (SUVmax), and the true positive rate of the lesions were compared. Furthermore, the FAPI uptake in nodular-like pulmonary lesions (d<3cm) and those with irregular borders was evaluated across the groups. A correlation analysis sought to understand the relationship between FAPI uptake in primary and pulmonary metastatic lesions. Results: The study's participants were composed of 52 males and 47 females, with an average age of 56.8 ± 13.2 years. A higher uptake and detection rate for pulmonary lesions were exhibited by Group G1 compared to the other groups (SUVmax [G1 vs. G2 vs. G3: 9.1 ± 4.1 vs. 6.1 ± 4.1 vs. 5.3 ± 5.8], P<0.05; TBR [G1 vs. G2 vs. G3: 6.2 ± 2.4 vs. 4.1 ± 2.2 vs. 3.2 ± 2.7], P<0.01; true positive rate 95.1% vs. 88% vs. 75.6%]. In nodular-like lung lesions smaller than 3 cm, G1 showed a significantly higher FAPI uptake compared to G2 and G3 (SUVmax [G1 vs. G2 vs. G3: 8.8 ± 4.3 vs. 5.2 ± 3.2 vs. 4.9 ± 6.1], P<0.01; TBR [G1 vs. G2 vs. G3: 5.7 ± 2.7 vs. 3.7 ± 2.1 vs. 3.3 ± 4.4], P<0.05). Both G1 and G2 demonstrated significantly elevated FAPI agent activity in irregular-bordered pulmonary lesions when compared to G3 (SUVmax [G1 vs. G2 vs. G3: 10.9 ± 3.3 vs. 8.5 ± 2.7 vs. 4.6 ± 2.7], P<0.01; TBR [G1 vs. G2 vs. G3: 7.2 ± 2.1 vs. 6.4 ± 1.3 vs. 3.2 ± 2.4], P<0.01). A positive correlation was identified between the level of 68Ga-FAPI uptake in primary lesions and the uptake in pulmonary metastatic lesions within G2 (r=0.856, P<0.05). Conclusion: 68Ga-FAPI PET/CT imaging proves to be of significant value in the evaluation of pulmonary lesions, offering distinctive insights into their nature.

Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis.

BACKGROUND: This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC). METHODS: We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells. RESULTS: After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family. CONCLUSION: Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.