Clinicopathological, immunohistochemical and therapeutic approaches on survival in patients with epithelioid glioblastoma: Institutional experience in the management of 58 patients.

Epithelioid glioblastoma (Ep-GBM) is a rare variant of glioblastoma characterized by a high recurrence rate and poor prognosis. Currently, there is no established standard treatment for Ep-GBM. Therefore, we identified 58 Ep-GBM cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 30 male and 28 female patients with a median age of 39 years. Headaches and dizziness were the most common clinical symptom. The tumor is most frequently located in the temporal lobe (36.2%). The positivity rate for BRAF-V600E is 56.9% (33/58), for MGMT is 56.9% (33/58), and for INI-1 is 75% (30/40). Tumor recurrence was observed in 39 patients. The median progression-free survival (PFS) of all patients was 12.7 months, while the median overall survival (OS) was 29.1 months. Additionally, the median survival time after recurrence was 14.3 months. Both univariate and multivariate COX regression analyses revealed that individuals who received more than six cycles of adjuvant oral temozolomide experienced a longer median PFS compared to those who received fewer cycles. Characteristics associated with poorer PFS included tumor dissemination prior to initial surgery. Additionally, both analyses identified tumor dissemination, radiotherapy and adjuvant oral temozolomide as predictors of OS. Notably, for patients with recurrent Ep-GBM, reoperation was shown to significantly increase survival time after recurrence. In conclusion, the standard Stupp regimen is also applicable to patients with Ep-GBM, extending adjuvant oral temozolomide could further improve survival for Ep-GBM patients, reoperation may also prolong survival for recurrent Ep-GBM.

Puerarin: a hepatoprotective drug from bench to bedside.

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

Prediction of gestational diabetes mellitus by multiple biomarkers at early gestation.

BACKGROUND: It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. METHODS: This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11-14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. RESULTS: FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. CONCLUSION: The combination of FPG and IGFBP-2 at early gestation (11-14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.

[Effect of 2-phenylethyl-beta-glucopyranoside isolated from Huaizhong No. 1 Rehmannia glutinosa on hypoxic pulmonary hypertension by regulating PI3K/Akt/m TOR/HIF-1α pathway].

The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.

Restriction Spectrum Imaging and Diffusion Kurtosis Imaging for Assessing Proliferation Status in Rectal Carcinoma.

OBJECTIVES: To investigate the application of the three-compartment restriction spectrum imaging (RSI) model, diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in predicting Ki-67 status in rectal carcinoma. METHODS: A total of 80 rectal carcinoma patients, including 47 high-proliferation (Ki-67 > 50%) cases and 33 low-proliferation (Ki-67 ≤ 50%) cases, underwent pelvic MRI were enrolled. Parameters derived from RSI (f1, f2, and f3), DKI (MD and MK), and DWI (ADC) were calculated and compared between the two groups. Logistic regression (LR) analysis was conducted to identify independent predictors and assess combined diagnosis. Area under the receiver operating characteristic curve (AUC), DeLong analysis, and calibration curve analyses were performed to evaluate diagnostic performance. RESULTS: The patients with high-proliferation rectal carcinoma exhibited significantly higher f1 and MK values and significantly lower ADC, MD, f2, and f3 values than those with low-proliferation rectal carcinoma (P < 0.05). LR analysis showed that MD, MK, and f2 were independent predictors for Ki-67 status in rectal carcinoma. Moreover, the combination of these three parameters achieved an optimal diagnostic efficacy (AUC = 0.877, sensitivity = 80.85%, specificity = 84.85%) that was significantly better than that obtained using ADC (AUC = 0.783, Z = 2.347, P = 0.019), f2 (AUC = 0.732, Z = 2.762, P = 0.006), and f3 (AUC = 0.700, Z = 3.071, P = 0.002). The combined diagnosis also showed good performance (AUC = 0.859) in the internal validation analysis based on 1000 bootstrap samples, while the calibration curve demonstrated that the combined diagnosis provided good stability. CONCLUSION: RSI, DKI, and DWI can effectively differentiate between patients with high- and low-proliferation rectal carcinoma. Furthermore, the MD, MK, and f2 imaging parameters may be a novel and promising combination biomarker for examining Ki-67 status in rectal carcinoma.

Identification and transcriptome analysis of a photosynthesis deficient mutant of Populus davidiana Dode.

Photosynthesis is the main source of energy for plants to sustain growth and development. Abnormalities in photosynthesis may cause defects in plant development. The elaborate regulatory mechanism underlying photosynthesis remains unclear. In this study, we identified a natural mutant from the Greater Khingan Mountains and named it as "1-T". This mutant had variegated leaf with irregular distribution of yellow and green. Chlorophyll contents and photosynthetic capacity of 1-T were significantly reduced compared to other poplar genotypes. Furthermore, a transcriptome analysis revealed 3269 differentially expressed genes (DEGs) in 1-T. The products of the DEGs were enriched in photosystem I and photosystem II. Three motifs were significantly enriched in the promoters of these DEGs. Yeast one-hybrid, Electrophoretic mobility shift assays and tobacco transient transformation experiments indicated that PdGLKs may bind to the three motifs. Further analysis indicated that these photosystem related genes were also significantly down-regulated in PdGLK-RNAi poplars. Therefore, we preliminarily concluded that the down-regulation of PdGLKs in 1-T may affect the expression of photosystem-related genes, resulting in abnormal photosystem development and thus affecting the growth and development. Our results provide new insights into the molecular mechanism of photosynthesis regulating plant growth.

Improving Scalability of copper recovery in saline microbial fuel cells with microtubular polypyrrole-based cathodic electrocatalysts.

Microbial fuel cells (MFC) are emerging energy-efficient systems for copper (Cu) electrowinning from waste streams by coupling it with anodic oxidation of organics in wastewater. However, there is a lack of research examining scalable electrocatalysts for Cu electrowinning at low cathodic overpotentials in highly saline catholytes often found in e-waste leachates. The challenge of developing resilient anodic biofilms that withstand the antagonistic effects of ions migrating from catholytes in saline MFC also needs to be addressed. In this study, polypyrrole (PPy) cathodic electrocatalysts were developed and coupled with a robust halophilic anodic biofilm in MFC to improve the kinetics of Cu electrowinning from acidic chloride-based catholytes. Electrochemical characterisation of these cathodes revealed shuttling of electrons by redox-active PPy via the formation of intermediate Cu+-complexes as an energy-efficient pathway for producing metallic Cu. High power densities ranging from 0.63 ± 0.17 to 0.73 ± 0.05 W m-2 were achieved with undoped-PPy and phytic acid doped-PPy cathodes with simultaneous recovery of ∼97% Cu. These electrocatalysts also exhibited low charge transfer resistance (3-8 mΩ m2) that met the requisites for scalable cathodes in MFC. However, a decrease in the efficiency of PPy cathodes was observed over 5 d due to competing reactions at their interfaces, including re-oxidation of deposited Cu and cathodic corrosion, with further studies suggested to enhance their corrosion resistance. Nonetheless, integrating PPy electrocatalysts for Cu electrowinning in saline MFC has advanced its outlooks as an energy-efficient downstream process for urban mining of Cu from e-waste.

Tri-Compartmental Restriction Spectrum Imaging Based on 18F-FDG PET/MR for Identification of Primary Benign and Malignant Lung Lesions.

BACKGROUND: Restriction spectrum imaging (RSI), as an advanced quantitative diffusion-weighted magnetic resonance imaging technique, has the potential to distinguish primary benign and malignant lung lesions. OBJECTIVE: To explore how well the tri-compartmental RSI performs in distinguishing primary benign from malignant lung lesions compared with diffusion-weighted imaging (DWI), and to further explore whether positron emission tomography/magnetic resonance imaging (PET/MRI) can improve diagnostic efficacy. STUDY TYPE: Prospective. POPULATION: 137 patients, including 108 malignant and 29 benign lesions (85 males, 52 females; average age = 60.0 ± 10.0 years). FIELD STRENGTH/SEQUENCE: T2WI, T1WI, multi-b value DWI, MR-based attenuation correction, and PET imaging on a 3.0 T whole-body PET/MR system. ASSESSMENT: The apparent diffusion coefficient (ADC), RSI-derived parameters (restricted diffusion f 1 $$ {f}_1 $$ , hindered diffusion f 2 $$ {f}_2 $$ , and free diffusion f 3 $$ {f}_3 $$ ) and the maximum standardized uptake value (SUVmax) were calculated and analyzed for diagnostic efficacy individually or in combination. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, receiver operating characteristic (ROC) curves, Delong test, Spearman's correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The f 1 $$ {f}_1 $$ , SUVmax were significantly higher, and f 3 $$ {f}_3 $$ , ADC were significantly lower in the malignant group [0.717 ± 0.131, 9.125 (5.753, 13.058), 0.194 ± 0.099, 1.240 (0.972, 1.407)] compared to the benign group [0.504 ± 0.236, 3.390 (1.673, 6.030), 0.398 ± 0.195, 1.485 ± 0.382]. The area under the ROC curve (AUC) values ranked from highest to lowest as follows: AUC (SUVmax) > AUC ( f 3 $$ {f}_3 $$ ) > AUC ( f 1 $$ {f}_1 $$ ) > AUC (ADC) > AUC ( f 2 $$ {f}_2 $$ ) (AUC = 0.819, 0.811, 0.770, 0.745, 0549). The AUC (AUC = 0.900) of the combined model of RSI with PET was significantly higher than that of either single-modality imaging. CONCLUSION: RSI-derived parameters ( f 1 $$ {f}_1 $$ , f 3 $$ {f}_3 $$ ) might help to distinguish primary benign and malignant lung lesions and the discriminatory utility of f 2 $$ {f}_2 $$ was not observed. The RSI exhibits comparable or potentially enhanced performance compared with DWI, and the combined RSI and PET model might improve diagnostic efficacy. TECHNICAL EFFICACY: Stage 2.

Feature Matching of Microsecond-Pulsed Magnetic Fields Combined with Fe3O4 Particles for Killing A375 Melanoma Cells.

The combination of magnetic fields and magnetic nanoparticles (MNPs) to kill cancer cells by magneto-mechanical force represents a novel therapy, offering advantages such as non-invasiveness, among others. Pulsed magnetic fields (PMFs) hold promise for application in this therapy due to advantages such as easily adjustable parameters; however, they suffer from the drawback of narrow pulse width. In order to fully exploit the potential of PMFs and MNPs in this therapy, while maximizing therapeutic efficacy within the constraints of the narrow pulse width, a feature-matching theory is proposed, encompassing the matching of three aspects: (1) MNP volume and critical volume of Brownian relaxation, (2) relaxation time and pulse width, and (3) MNP shape and the intermittence of PMF. In the theory, a microsecond-PMF generator was developed, and four kinds of MNPs were selected for in vitro cell experiments. The results demonstrate that the killing rate of the experimental group meeting the requirements of the theory is at least 18% higher than the control group. This validates the accuracy of our theory and provides valuable guidance for the further application of PMFs in this therapy.

The effect of ultrasonic power on the physicochemical properties and antioxidant activities of frosted figs pectin.

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification.

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

Amide proton transfer-weighted imaging and stretch-exponential model DWI based 18F-FDG PET/MRI for differentiation of benign and malignant solitary pulmonary lesions.

OBJECTIVES: To differentiate benign and malignant solitary pulmonary lesions (SPLs) by amide proton transfer-weighted imaging (APTWI), mono-exponential model DWI (MEM-DWI), stretched exponential model DWI (SEM-DWI), and 18F-FDG PET-derived parameters. METHODS: A total of 120 SPLs patients underwent chest 18F-FDG PET/MRI were enrolled, including 84 in the training set (28 benign and 56 malignant) and 36 in the test set (13 benign and 23 malignant). MTRasym(3.5 ppm), ADC, DDC, α, SUVmax, MTV, and TLG were compared. The area under receiver-operator characteristic curve (AUC) was used to assess diagnostic efficacy. The Logistic regression analysis was used to identify independent predictors and establish prediction model. RESULTS: SUVmax, MTV, TLG, α, and MTRasym(3.5 ppm) values were significantly lower and ADC, DDC values were significantly higher in benign SPLs than malignant SPLs (all P < 0.01). SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors. Within the training set, the prediction model based on these independent predictors demonstrated optimal diagnostic efficacy (AUC, 0.976; sensitivity, 94.64%; specificity, 92.86%), surpassing any single parameter with statistical significance. Similarly, within the test set, the prediction model exhibited optimal diagnostic efficacy. The calibration curves and DCA revealed that the prediction model not only had good consistency but was also able to provide a significant benefit to the related patients, both in the training and test sets. CONCLUSION: The SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors for differentiation of benign and malignant SPLs, and the prediction model based on them had an optimal diagnostic efficacy.

Characterization of oxylipins in Antarctic krill oil (Euphausia superba) during storage based on RPLC-MS/MS analysis.

Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids (PUFAs), but is prone to oxidative degradation, resulting in the formation of oxylipins, which compromise AKO quality. Herein, we used reversed-phase-high performance liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) to perform qualitative and semi-quantitative analyses of oxylipins in AKO during storage. A total of 27 oxylipins were identified. A notable decrease in epoxy oxylipins (from 41.8 % to 26.9 % of the total oxylipins) was observed, whereas the content of dihydro oxylipins initially increased and then decreased with 48 h, as a pivotal point for AKO quality decline during storage. We suspected that the ratio of dihydroxyl and epoxy oxylipins could be a novel oxidative index to evaluate the oxidation of AKO. Statistical analysis allowed the identification of five oxylipins which showed unique correlations with various indexes. The findings discussed herein provide important new insights into mechanisms of oxidation occurring in AKO during storage.

Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. AIM OF THE STUDY: To investigate F.S in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. RESULTS: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. CONCLUSION: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.

The role of dynamic, static, and delayed total-body PET imaging in the detection and differential diagnosis of oncological lesions.

OBJECTIVES: Commercialized total-body PET scanners can provide high-quality images due to its ultra-high sensitivity. We compared the dynamic, regular static, and delayed 18F-fluorodeoxyglucose (FDG) scans to detect lesions in oncologic patients on a total-body PET/CT scanner. MATERIALS & METHODS: In all, 45 patients were scanned continuously for the first 60 min, followed by a delayed acquisition. FDG metabolic rate was calculated from dynamic data using full compartmental modeling, whereas regular static and delayed SUV images were obtained approximately 60- and 145-min post-injection, respectively. The retention index was computed from static and delayed measures for all lesions. Pearson's correlation and Kruskal-Wallis tests were used to compare parameters. RESULTS: The number of lesions was largely identical between the three protocols, except MRFDG and delayed images on total-body PET only detected 4 and 2 more lesions, respectively (85 total). FDG metabolic rate (MRFDG) image-derived contrast-to-noise ratio and target-to-background ratio were significantly higher than those from static standardized uptake value (SUV) images (P < 0.01), but this is not the case for the delayed images (P > 0.05). Dynamic protocol did not significantly differentiate between benign and malignant lesions just like regular SUV, delayed SUV, and retention index. CONCLUSION: The potential quantitative advantages of dynamic imaging may not improve lesion detection and differential diagnosis significantly on a total-body PET/CT scanner. The same conclusion applied to delayed imaging. This suggested the added benefits of complex imaging protocols must be weighed against the complex implementation in the future. CLINICAL RELEVANCE: Total-body PET/CT was known to significantly improve the PET image quality due to its ultra-high sensitivity. However, whether the dynamic and delay imaging on total-body scanner could show additional clinical benefits is largely unknown. Head-to-head comparison between two protocols is relevant to oncological management.

An [18F]FDG PET/3D-ultrashort echo time MRI-based radiomics model established by machine learning facilitates preoperative assessment of lymph node status in non-small cell lung cancer.

OBJECTIVES: To develop an [18F]FDG PET/3D-UTE model based on clinical factors, three-dimensional ultrashort echo time (3D-UTE), and PET radiomics features via machine learning for the assessment of lymph node (LN) status in non-small cell lung cancer (NSCLC). METHODS: A total of 145 NSCLC patients (training, 101 cases; test, 44 cases) underwent whole-body [18F]FDG PET/CT and chest [18F]FDG PET/MRI were enrolled. Preoperative clinical factors and 3D-UTE, CT, and PET radiomics features were analyzed. The Mann-Whitney U test, LASSO regression, and SelectKBest were used for feature extraction. Five machine learning algorithms were used to establish prediction models, which were evaluated by the area under receiver-operator characteristic (ROC), DeLong test, calibration curves, and decision curve analysis (DCA). RESULTS: A prediction model based on random forest, consisting of four clinical factors, six 3D-UTE, and six PET radiomics features, was used as the final model for PET/3D-UTE. The AUCs of this model were 0.912 and 0.791 in the training and test sets, respectively, which not only showed different degrees of improvement over individual models such as clinical, 3D-UTE, and PET (AUC-training = 0.838, 0.834, and 0.828, AUC-test = 0.756, 0.745, and 0.768, respectively) but also achieved the similar diagnostic efficacy as the optimal PET/CT model (AUC-training = 0.890, AUC-test = 0.793). The calibration curves and DCA indicated good consistency (C-index, 0.912) and clinical utility of this model, respectively. CONCLUSION: The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using machine learning methods could noninvasively assess the LN status of NSCLC. CLINICAL RELEVANCE STATEMENT: A machine learning model of 18F-fluorodeoxyglucose positron emission tomography/ three-dimensional ultrashort echo time could noninvasively assess the lymph node status of non-small cell lung cancer, which provides a novel method with less radiation burden for clinical practice. KEY POINTS: • The 3D-UTE radiomics model using the PLS-DA classifier was significantly associated with LN status in NSCLC and has similar diagnostic performance as the clinical, CT, and PET models. • The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using the RF classifier could noninvasively assess the LN status of NSCLC and showed improved diagnostic performance compared to the clinical, 3D-UTE, and PET models. • In the assessment of LN status in NSCLC, the [18F]FDG PET/3D-UTE model has similar diagnostic efficacy as the [18F]FDG PET/CT model that incorporates clinical factors and CT and PET radiomics features.

DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3K-Akt-NF-κB pathway.

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.

Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway.

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin ß3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention.

Value evaluation of serum (sdLDLc*HCYc)/HDLc ratio in the stability of intracranial arterial plaques in patients with acute cerebral infarction.

BACKGROUND: We aimed to analyze the value of serum (sdLDLc*HCYc)/HDLc ratio in the stability of intracranial arterial plaques among patients with acute cerebral infarction. METHODS: A retrospective analysis was conducted on 140 patients with acute cerebral infarction admitted to the neurology department and 101 healthy individuals for regular examinations in our hospital from 2013 to 2019, who were respectively allocated into the study group and the control group. Participants in both groups were measured for serum sdLDLc, HDLc, and HCYc using peroxidase method, enzyme-linked immunosorbent assay, and enzyme method, respectively. The laboratory indexes of the two groups were compared. The multivariate logistic regression analysis was done to analyze the influencing factors of the stability of intracranial artery plaque in patients with acute cerebral infarction. The value of high-density lipoprotein cholesterol (HDL-C), homocysteine, sdLDLc, (sdLDLc*HCYc)/HDLc in diagnosing the stability of intracranial artery plaque was also evaluated in patients with acute cerebral infarction. RESULTS: There was no distinct difference in height, hypertension, diabetes, coronary heart disease, smoking history and drinking history between the two groups (P>0.05). The study group showed statistically significant differences in age, gender, weight, and BMI (P<0.05). The current study demonstrated no statistical difference in the levels of TG, low-density lipoprotein cholesterol (LDL-C), α-lipoprotein, and HCYc between the two groups (P>0.05). However, the levels of TC, HDL-C, sdLDLc, (sdLDLc*HCYc)/HDLc in the study group were significantly different when comparing with the control group (P<0.05). No statistically significant difference was found in the levels of TG, triglycerides, LDL-C, α-lipoprotein, and HCYc among patients with different degrees of stenosis in the study group (P>0.05). The level of HDL-C was significantly lower in cases of severe stenosis compared to no stenosis, mild stenosis and moderate stenosis, with severe stenosis showing the lowest levels; mild stenosis had lower levels than no stenosis, while moderate stenosis had lower levels than both no stenosis and mild stenosis (P<0.05). The levels of sdLDLc, (sdLDLc*HCYc)/HDLc exhibited a significant increase in cases of severe stenosis as compared tono stenosis, mild stenosis, and moderate stenosis. Furthermore, the levels of sdLDLc, (sdLDLc*HCYc)/HDLc were found to be higher in moderate stenosis as compared to no stenosis and mild stenosis. Similarly, the levels of sdLDLc, (sdLDLc*HCYc)/HDLc were observed to be higher in mild stenosis than no stenosis (P<0.05).The independent variables were set as the indicators with difference in single factor comparison, including age, gender, BMI, TC, LDL-C, HDL-C, HCYc, sdLDLc, (sdLDLc*HCYc)/HDLc. The dependent variable was the stability of intracranial artery plaque in patients with acute cerebral infarction. After variable selection, the results showed that the factors influencing the stability of intracranial artery plaque in patients with acute cerebral infarction were age, BMI, (sdLDLc*HCYc)/HDLc. The degree of plaque enhancement was used as a criterion to reflect the stability of plaque. ROC curve analysis showed that (sdLDLc*HCYc)/HDLc had a higher evaluation value for the stability of intracranial artery plaque than HDL-C, homocysteine, and sdLDLc in patients with acute cerebral infarction. CONCLUSION: The serum (sdLDLc*HCYc)/HDLc ratio was found to have potential in evaluating the stability of intracranial arterial plaques in patients with acute cerebral infarction.