Novel [68Ga/177Lu]Ga/Lu-AZ-093 as PSMA-Targeting Agent for Diagnosis and Radiotherapy.

Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer cells can serve as a target for imaging and radioligand therapy (RLT). Previously, [68Ga]Ga-P16-093, containing a Ga(III) chelator, N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), displayed excellent PSMA-targeting properties and showed a high tumor uptake and retention useful for diagnosis in prostate cancer patients. Recently, [177Lu]Lu-PSMA-617 has been approved by the U.S. food and drug administration (FDA) for the treatment of prostate cancer patients. Derivatives of PSMA-093 using AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid), as the chelator, were designed as alternative agents forming complexes with both diagnostic and therapeutic radiometals, such as gallium-68 (log K = 22.18) or lutetium-177 (log K = 21.85). The aim of this study is to evaluate AAZTA-Gly-O-(methylcarboxy)-Tyr-Phe-Lys-NH-CO-NH-Glu (designated as AZ-093, 1) leading to a gallium-68/lutetium-177 theranostic pair as potential PSMA targeting agents. Synthesis of the desired precursor, AZ-093, 1, was effectively accomplished. Labeling with either [68Ga]GaCl3 or [177Lu]LuCl3 in a sodium acetate buffer solution (pH 4-5) at 50 °C in 5 to 15 min produced either [68Ga]Ga-1 or [177Lu]Lu-1 with high yields and excellent radiochemical purities. Results of in vitro binding studies, cell uptake, and retention (using PSMA-positive prostate carcinoma cells line, 22Rv1-FOLH1-oe) were comparable to that of [68Ga]Ga-P16-093 and [177Lu]Lu-PSMA-617, respectively. Specific cellular uptake was determined with or without the competitive blocking agent (2 µM of "cold" PSMA-11). Cellular binding and internalization showed a time-dependent increase over 2 h at 37 °C in the PSMA-positive cells. The cell uptakes were completely blocked by the "cold" PSMA-11 suggesting that they are competing for the same PSMA binding sites. In the mouse model with implanted PSMA-positive tumor cells, both [68Ga]Ga-1 and [177Lu]Lu-1 displayed excellent uptake and retention in the tumor. Results indicate that [68Ga]Ga/[177Lu]Lu-1 (68Ga]Ga/[177Lu]Lu-AZ-093) is potentially useful as PSMA-targeting agent for both diagnosis and radiotherapy of prostate cancer.

Paeoniae radix rubra:A review of ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control.

Paeoniae Radix Rubra (PRR) known as Chishao, in China, is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, with a history of over 2000 years in traditional Chinese medicine, is employed to clear heat, cool the blood, dispel blood stasis, and alleviate pain. Phytochemical investigations identified 264 compounds that contained monoterpenes and their glycosides, sesquiterpenes, triterpenes, steroids, flavonoids, lignans, tannins, volatile oils, and other compounds. It has been reported to have different pharmacological activities, including cardiovascular-protective, antidepressive, neuroprotective, antitumor, hepatoprotective, and anti-inflammatory effects. This study offers a comprehensive review covering ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control of PRR. The comprehensive analysis aims to achieve a thorough understanding of its effects and serves as a foundation for future research and development.

Association between heme oxygenase-1 and hyperlipidemia in pre-diabetic patients: a cross-sectional study.

Background: Although the importance and benefit of heme oxygenase-1 (HO-1) in diabetes rodent models has been known, the contribution of HO-1 in the pre-diabetic patients with hyperlipidemia risk still remains unclear. This cross-sectional study aims to evaluate whether HO-1 is associated with hyperlipidemia in pre-diabetes. Methods: Serum level of HO-1 was detected using commercially available ELISA kit among 1,425 participants aged 49.3-63.9 with pre-diabetes in a multicenter Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) prospective observational study. Levels of total cholesterol (TC) and triglyceride (TG) were measured and used to defined hyperlipidemia. The association between HO-1 and hyperlipidemia was explored in different subgroups. Result: The level of HO-1 in pre-diabetic patients with hyperlipidemia (181.72 ± 309.57 pg/ml) was obviously lower than that in pre-diabetic patients without hyperlipidemia (322.95 ± 456.37 pg/ml). High level of HO-1 [(210.18,1,746.18) pg/ml] was negatively associated with hyperlipidemia (OR, 0.60; 95% CI, 0.37-0.97; p = 0.0367) after we adjusted potential confounding factors. In subgroup analysis, high level of HO-1 was negatively associated with hyperlipidemia in overweight pre-diabetic patients (OR, 0.50; 95% CI, 0.3-0.9; p = 0.034), especially in overweight women (OR, 0.42; 95% CI, 0.21-0.84; p = 0.014). Conclusions: In conclusion, elevated HO-1 level was negatively associated with risk of hyperlipidemia in overweight pre-diabetic patients, especially in female ones. Our findings provide information on the exploratory study of the mechanism of HO-1 in hyperlipidemia, while also suggesting that its mechanism may be influenced by body weight and gender.

Carrier-free chemo-phototherapeutic nanomedicines with endo/lysosomal escape function enhance the therapeutic effect of drug molecules in tumors.

Carrier-free nanomedicines offer advantages of extremely high drug loading capacity (>80%), minimal non-drug constituent burden, and facile preparation processes. Numerous studies have proved that multimodal cancer therapy can enhance chemotherapy efficiency and mitigate multi-drug resistance (MDR) through synergistic therapeutic effects. Upon penetration into the tumor matrix, nanoparticles (NPs) are anticipated to be uptaken by cancer cells, primarily through clathrin-meditated endocytosis pathways, leading to their accumulation in endosomes/lysosomes within cells. However, endo/lysosomes exhibit a highly degradative environment for organic NPs and drug molecules, often resulting in treatment failure. Hence, this study designed a lysosomal escape mechanism with carrier-free nanomedicine, combining the chemotherapeutic drug, curcumin (Cur), and the photothermal/photodynamic therapeutic drug, indocyanine green (ICG), for synergistic cancer treatment (ICG-Cur NPs) via a facile preparation process. To facilitate endo/lysosomal escape, ICG-Cur NPs were modified with metal-phenolic networks (MPNs) of different thickness. The results indicate that a thick MPN coating promotes rapid endo/lysosomal escape of ICG-Cur NPs within 4 h and enhances the photothermal conversion efficiency of ICG-Cur NPs by 55.8%, significantly improving anticancer efficacy in both chemo- and photo-therapies within 3D solid tumor models. This finding underscores the critical role of endo/lysosomal escape capacity in carrier-free drug NPs for therapeutic outcomes and offers a facile solution to achieve it.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Exploring online consumer behavior on fraudulent energy-saving products.

Purchasing energy-saving products is key for public participation in energy conservation and sustainable development. However, the sale of fraudulent energy-saving products has boomed through online shopping, with little research on these products and consumer demands. This study explored the underlying factors driving consumer purchases of fraudulent energy-saving products and measured their impact on environmental awareness. Sales data for such products from four major online shopping platforms were collected. Results suggested unique demand characteristics from consumers who unknowingly purchase fraudulent energy-saving products, referred to as "hidden energy savers", including a preference for moderately priced products, a desire for straightforward energy-saving explanations, and a tendency to seek multiple additional features, even if they conflict with the core functionality. Perceived installation and usage difficulty significantly influences purchasing behavior. A practical survey of freight companies and individual transporters' demand for freight energy-saving products was conducted as a case study to validate the practical application of this research. This study presents a novel perspective on public energy-saving behavior, aiding in creating true energy-saving products, boosting public energy conservation interest, and reducing the negative impact of fraudulent products on environmental awareness. It also sheds light on hidden consumer needs, guiding the development of authentic energy-saving products.

A retrospective study on the analysis of influencing factors of neutropenia in endometrial cancer with adjuvant chemoradiotherapy.

OBJECTIVE: This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT). METHODS: Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 109/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled. RESULTS: A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701-0.976), ANC (OR = 0.749; 95%CI, 0.586-0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008-0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741-0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130-4.618) were associated with neutropenia with adjuvant CRT for EC (p < 0.05), results of multifactorial GEE analysis showed that before adjuvant CRT ANC (OR = 0.552; 95%CI, 0.973-2.231), AMC (OR = 0.047; 95%CI, 0.004-0.052), platinum/docetaxel (OR = 2.437; 95%CI, 1.087-5.464) were an independent influence on neutropenia in adjuvant CRT for EC (p < 0.05). Multifactorial Logistic regression shows addition of radiotherapy to the first cycle of chemotherapy (OR = 4.413; 95%CI, 1.238-18.891) was an independent influence of neutropenia (p < 0.05). CONCLUSIONS: Patients with low pre-CRT ANC and AMC, platinum/docetaxel dosing regimens need to be closely monitored during each cycle of CRT. Also, the concurrent addition of radiotherapy should be avoided during the first cycle of chemotherapy.

A high-quality dataset featuring classified and annotated cervical spine X-ray atlas.

Recent research in computational imaging largely focuses on developing machine learning (ML) techniques for image recognition in the medical field, which requires large-scale and high-quality training datasets consisting of raw images and annotated images. However, suitable experimental datasets for cervical spine X-ray are scarce. We fill the gap by providing an open-access Cervical Spine X-ray Atlas (CSXA), which includes 4963 raw PNG images and 4963 annotated images with JSON format (JavaScript Object Notation). Every image in the CSXA is enriched with gender, age, pixel equivalent, asymptomatic and symptomatic classifications, cervical curvature categorization and 118 quantitative parameters. Subsequently, an efficient algorithm has developed to transform 23 keypoints in images into 77 quantitative parameters for cervical spine disease diagnosis and treatment. The algorithm's development is intended to assist future researchers in repurposing annotated images for the advancement of machine learning techniques across various image recognition tasks. The CSXA and algorithm are open-access with the intention of aiding the research communities in experiment replication and advancing the field of medical imaging in cervical spine.

Keratinocyte-derived small extracellular vesicles delay diabetic wound healing by triggering fibroblasts autophagy.

Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.

Diabetic foot ulcers are a serious complication of diabetes and can lead to amputation and death. Therefore, it is crucial to comprehensively elucidate the mechanisms of delayed diabetic wound healing, with emphasis on the role of keratinocyte-derived small extracellular vesicles. In vivo and in vitro experiments showed that keratinocyte-derived small extracellular vesicles suppressed diabetic wound healing, which is partly attributed to the effects of their content (LINC01435) in fibroblasts. This study suggests that LINC01435 could be targeted to regulate diabetic wound healing.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities: The FOCUS Randomized Clinical Trial.

Importance: Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. Objective: To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Intervention: Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. Main Outcomes and Measures: The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. Results: A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. Conclusions and Relevance: The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Trial Registration: Chinese Clinical Trial Register: ChiCTR1900023241.

Comprehensive analysis of the oral microbiota and metabolome change in patients of burning mouth syndrome with psychiatric symptoms.

Background: Burning mouth syndrome (BMS) is a chronic idiopathic facial pain with intraoral burning or dysesthesia. BMS patients regularly suffer from anxiety/depression, and the association of psychiatric symptoms with BMS has received considerable attention in recent years. The aims of this study were to investigate the potential interplay between psychiatric symptoms and BMS. Methods: Using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS) to evaluate the oral microbiota and saliva metabolism of 40 BMS patients [including 29 BMS patients with depression or anxiety symptoms (DBMS)] and 40 age matched healthy control (HC). Results: The oral microbiota composition in BMS exhibited no significant differences from HC, although DBMS manifested decreased α-diversity relative to HC. Noteworthy was the discernible elevation in the abundance of proinflammatory microorganisms within the oral microbiome of individuals with DBMS. Parallel findings in LC/MS analyses revealed discernible disparities in metabolites between DBMS and HC groups. Principal differential metabolites were notably enriched in amino acid metabolism and lipid metabolism, exhibiting associations with infectious and immunological diseases. Furthermore, the integrated analysis underscores a definitive association between the oral microbiome and metabolism in DBMS. Conclusions: This study suggests possible future modalities for better understanding the pathogenesis and personalized treatment plans of BMS.

Exhaled Breath Analysis for The Discrimination of Asthma and Chronic Obstructive Pulmonary Disease.

Abstract BACKGROUND Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic respiratory diseases. In middle-aged and elderly patients, it is difficult to distinguish between COPD and asthma based on clinical symptoms and pulmonary function examinations in clinical practice. Thus, an accurate and reliable inspection method is required. METHOD In this study, we aimed to identify breath biomarkers and evaluate the accuracy of breathomics-based methods for discriminating between COPD and asthma. In this multi-center cross-sectional study, exhaled breath samples were collected from 89 patients with COPD and 73 with asthma and detected on a high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform from October 20, 2022, to May 20, 2023, in four hospitals. Data analysis was performed from June 15, 2023, to August 16, 2023. The sensitivity, specificity, and accuracy were calculated to assess the overall performance of the VOC-based COPD and asthma discrimination models. Potential VOC markers related to COPD and asthma were also analyzed. RESULTS The age of all participants ranged from to 18-86 years, and 54 (33.3%) were men. Based on breathomics feature selection, ten VOCs were identified as COPD and asthma discrimination biomarkers via breath testing. The joint panel of these ten VOCs achieved an area under the curve (AUC) of 0.843, sensitivity of 75.9%, specificity of 87.5%, and accuracy of 80.0% in COPD and asthma discrimination. Furthermore, the VOCs detected in the breath samples were closely related to the clinical characteristics of COPD and asthma. CONCLUSIONS The VOC-based COPD and asthma discrimination model showed good accuracy, providing a new strategy for clinical diagnosis. Breathomics-based methods may play an important role in the diagnosis of COPD and asthma.

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase.

DDB1-Cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognizes and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Dcaf2 mainly expressed in germ cells of human and mouse. Our study found that Dcaf2 was expressed in mouse spermatogonia and spermatocyte. The depletion of Dcaf2 in germ cells by crossing Dcaf2fl/fl mice with stimulated by retinoic acid gene 8(Stra8)-Cre mice caused a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further studies showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins, cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG), decreasing of cell proliferation, increasing of DNA damage and apoptosis. Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells, which is exacerbated by co-overexpression of p21 and TDG. The findings indicate that DCAF2 maintains the proliferation and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG during the S phase.

Carbene-mediated gelatin and hyaluronic acid hydrogel paints with ultra adhesive ability for arthroscopic cartilage repair.

In articular cartilage defect, particularly in arthroscopy, regenerative hydrogels are urgently needed. It should be able to firmly adhere to the cartilage tissue and maintain sufficient mechanical strength to withstand approximately 10 kPa of arthroscopic hydraulic flushing. In this study, we report a carbene-mediated ultra adhesive hybrid hydrogel paints for arthroscopic cartilage repair, which combined the photo initiation of double crosslinking system with the addition of diatomite, as a further reinforcing agent and biological inorganic substances. The double network consisting of ultraviolet initiated polymerization of hyaluronic acid methacrylate (HAMA) and carbene insertion chemistry of diazirine-grafted gelatin (GelDA) formed an ultra-strong adhesive hydrogel paint (H2G5DE). Diatomite helped the H2G5DE hydrogel paint firmly adhere to the cartilage defect, withstanding nearly 100 kPa of hydraulic pressure, almost 10 times that in clinical arthroscopy. Furthermore, the H2G5DE hydrogel supported cell growth, proliferation, and migration, thus successfully repairing cartilage defects. Overall, this study demonstrates a proof-of-concept of ultra-adhesive polysaccharide hydrogel paints, which can firmly adhere to the articular cartilage defects, can resist continuous hydraulic pressure, can promote effective cartilage regeneration, and is very suitable for minimally invasive arthroscopy.

Pleural carbohydrate antigen 50 and malignant pleural effusion: a prospective, double-blind diagnostic accuracy test.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes. Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA). Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL). Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE.

Selective Solid-Liquid Extraction of Lithium Cation Using Tripodal Sulfate-Binding Receptors Driven by Electrostatic Interactions.

Owing to the important role of and increasing demand for lithium resources, lithium extraction is crucial. The use of molecular extractants is a promising strategy for selective lithium recovery, in which the interaction between lithium and the designed extractant can be manipulated at the molecular level. Herein, we demonstrate that anion receptors of tripodal hexaureas can selectively extract Li2SO4 solids into water containing DMSO (0.8% water) compared to other alkali metal sulfates. The hexaurea receptor with terminal hexyl chains displays the best Li+ extraction selectivity at 2-fold over Na+ and 12.5-fold over K+. The driving force underpinning selective lithium extraction is due to the combined interactions of Li+-SO42- electrostatics and the ion-dipole interaction of the lithium-receptor (carbonyl groups and N atoms); the latter was found to be cation size dependent, as supported by computational calculations. This work indicates that anion binding receptors could drive selective cation extraction, thus providing new insights into the design of receptors for ion recognition and separation.

Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). Methods: We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. Results: We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Conclusion: Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

Higher inflammatory response in hepatocellular carcinoma is associated with immune cell infiltration and a better outcome.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC. METHODS: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the "INFLAMMATORY_RESPONSE" gene set. RESULTS: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p < 0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p < 0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p < 0.01) and cytolytic activity (p < 0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p = 0.034) and overall survival in GSE76427 (p = 0.008). CONCLUSION: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and showed a trend toward a better patient prognosis.

Current status of sevoflurane anesthesia in association with microglia inflammation and neurodegenerative diseases.

Sevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and anti-inflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.

miR-4443 Contained Extracellular Vesicles: A Factor for Endometriosis Progression by PI3K/AKT/ACSS2 Cascade in-vitro.

Introduction: Endometriosis (EM) is an estrogen-dependent benign gynecologic disease affecting approximately 10% of reproductive-age women with a high recurrence rate, but lacks reliable biomarkers. No previous studies have investigated the possible use of extracellular vesicle (EV)-associated micro RNAs (miRNAs) from menstrual blood (MB) as candidate diagnostic or prognostic markers of EM. Methods: Specimens were obtained from endometriosis and non-endometriosis patients at the International Peace Maternity and Child Health Hospital in Shanghai. Microarray was used to screen differentially expressed miRNAs among peritoneal fluid (PF), fallopian tube fluid (FF), and MB. Dual-luciferase reporter gene assay was carried out to verify the relationship between miR-4443 and ACSS2. Cell proliferation and Transwell invasion assays were performed in vitro after intervention on miR-4443 and ACSS2 in hEM15A human endometrial stromal cells and primary human endometrial stromal cells (hESCs). Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and survival analysis were applied to clinical data, including severity of symptoms and relapse of EM among EM patients. Results: EV-associated miR-4443 was abundant in MB of endometriosis patients. ACSS2 knockdown and miR-4443 overexpression promoted cell proliferation and migration via the PI3K/AKT pathway. miR-4443 levels in MB-EVs were positively correlated with the degree of dyspareunia (r=0.64; P<0.0001) and dysmenorrhea (r=0.42; P<0.01) in the endometriosis group. ROC curve analyses showed an area under the curve (AUC) of 0.741 (95% CI 0.624-0.858; P<0.05) for miR-4443 and an AUC of 0.929 (95% CI 0.880-0.978; P<0.05) for the combination of miR-4443 and dysmenorrhea. Conclusion: MB-derived EV-associated miR-4443 might participate in endometriosis development, thus providing a new candidate biomarker for the noninvasive prediction of endometriosis recurrence.