Success rate of current human-derived gastric cancer organoids establishment and influencing factors: A systematic review and meta-analysis.

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

Bibliometrics analysis based on the Web of Science: Current trends and perspective of gastric organoid during 2010-2023.

BACKGROUND: Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. AIM: To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. METHODS: This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. RESULTS: A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. CONCLUSION: Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.

"Cell Disk" DNA Storage System Capable of Random Reading and Rewriting.

DNA has emerged as an appealing material for information storage due to its great storage density and durability. Random reading and rewriting are essential tasks for practical large-scale data storage. However, they are currently difficult to implement simultaneously in a single DNA-based storage system, strongly limiting their practicability. Here, a "Cell Disk" storage system is presented, achieving high-density in vivo DNA data storage that enables both random reading and rewriting. In this system, each yeast cell is used as a chamber to store information, similar to a "disk block" but with the ability to self-replicate. Specifically, each genome of yeast cell has a customized CRISPR/Cas9-based "lock-and-key" module inserted, which allows selective retrieval, erasure, or rewriting of the targeted cell "block" from a pool of cells ("disk"). Additionally, a codec algorithm with lossless compression ability is developed to improve the information density of each cell "block". As a proof of concept, target-specific reading and rewriting of the compressed data from a mimic cell "disk" comprising up to 105 "blocks" are demonstrated and achieve high specificity and reliability. The "Cell Disk" system described here concurrently supports random reading and rewriting, and it should have great scalability for practical data storage use.

Bi-Directional H-Bonding Modulated Soft/Hard Polyethylene Glycol-Polyaniline Coated Si-Anode for High-Performance Li-Ion Batteries.

Ultrahigh-capacity silicon (Si) anodes are essential for the escalating energy demands driven by the booming e-transportation and energy storage field. However, their practical applications are strictly hampered by their intrinsically low electroconductivity, sluggish Li-ion diffusion, and undesirably large volume change. Herein, a high-performance Si anode, comprised of a modulated soft/hard coating of polyethylene glycol (PEG) (as Li-ion conductor) and polyaniline (PANI) (as electron conductor) on the surface of Si nanoparticles (NPs) through H-bonding network, is introduced. In this design, the abundant ─OH groups of soft PEG allow it to uniformly cover Si NPs while the hard PANI binds to PEG through its ─N─H group, thus constructing a tight connectin between Si and PEG-PANI (PP). Consequently, the elastic PP allows Si@PP to accommodate the huge volume expansion while possessing fine electronic/ionic conductivity. Therefore, the Si@PP anode exhibits a high initial Coulombic efficiency of 90.5% and a stable capacity of 1871 mAh g-1 after 100 cycles at 1 A g-1 with a retention of 85.7%. Additionally, the Si@PP anode also demonstrates a high areal capacity of 3.01 mAh cm-2 after 100 cycles at 0.5 A g-1 . This work reveals a scalable interface design of multi-layer multifunctional coatings for high-performance electrode materials in next-generation Li-ion batteries.

A bacteriophage against Citrobacter braakii and its synergistic effect with antibiotics.

A bacteriophage BD49 specific for Citrobacter braakii was screened out and purified by double-layer plate method. It consists of a polyhedral head of 93.1 ± 1.2 nm long and 72.9 ± 4.2 nm wide, tail fibers, collar, sheath and baseplate. The bacteriophage was identified by morphology observed with transmission electron microscope (TEM), whole genome sequencing carried out by Illumina next generation sequencing (NGS) technique, and gene annotation based on Clusters of Orthologous Groups of proteins (COG) database. It was identified primarily as a member of Caudovirales by morphology and further determined as Caudovirales, Myoviridae, and Citrobacter bacteriophage by alignment of its whole genome sequence with the NCBI database and establishment of phylogenetic tree. The bacteriophage showed good environmental suitability with optimal multiplicity of infection (MOI) of 0.01, proliferation time of 80 min, optimum living temperature of 30-40 °C, and living pH of 5-10. In addition, it exhibited synergistic effect with ciprofloxacin against C. braakii in antibacterial tests.

Chaihu Shugan Powder inhibits interstitial cells of cajal mitophagy through USP30 in the treatment of functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study. AIM OF STUDY: The aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy. MATERIALS AND METHODS: The tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy. RESULTS: Animal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3Ⅱ/LC3Ⅰ、PINK1、Parkin、PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy. CONCLUSIONS: These results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the up-regulation of via PINK1/Parkin pathway.

Biological roles of soil microbial consortium on promoting safe crop production in heavy metal(loid) contaminated soil: A systematic review.

Heavy metal(loid) (HM) pollution of agricultural soils is a growing global environmental concern that affects planetary health. Numerous studies have shown that soil microbial consortia can inhibit the accumulation of HMs in crops. However, our current understanding of the effects and mechanisms of inhibition is fragmented. In this review, we summarise extant studies and knowledge to provide a comprehensive view of HM toxicity on crop growth and development at the biological, cellular and the molecular levels. In a meta-analysis, we find that microbial consortia can improve crop resistance and reduce HM uptake, which in turn promotes healthy crop growth, demonstrating that microbial consortia are more effective than single microorganisms. We then review three main mechanisms by which microbial consortia reduce the toxicity of HMs to crops and inhibit HMs accumulation in crops: 1) reducing the bioavailability of HMs in soil (e.g. biosorption, bioaccumulation and biotransformation); 2) improving crop resistance to HMs (e.g. facilitating the absorption of nutrients); and 3) synergistic effects between microorganisms. Finally, we discuss the prospects of microbial consortium applications in simultaneous crop safety production and soil remediation, indicating that they play a key role in sustainable agricultural development, and conclude by identifying research challenges and future directions for the microbial consortium to promote safe crop production.

The dynamic nexus: exploring the interplay of BMI before, during, and after pregnancy with Metabolic Syndrome (MetS) risk in Chinese lactating women.

BACKGROUND AND AIM: The health implications of BMI and MetS in lactating women are significant. This study aims to investigate the relationship between risk of Mets in lactation and BMI in four stages: pre-pregnancy, prenatal period, 42 days postpartum, and current lactation. METHODS AND RESULTS: A total of 1870 Lactating Women within 2 years after delivery were included from "China Child and Lactating Mother Nutrition Health Surveillance (2016-2017)". Logistic regression model and Restricted cubic spline (RCS) were used to estimate the relationship between BMI and risk of MetS. ROC analysis was used to determine the threshold for the risk of MetS. Chain mediating effect analysis was used to verify the mediating effect. BMI of MetS group in all stages were higher than non-MetS group (P < 0.0001). There were significant positive correlations between BMI in each stage and ORs of MetS during lactation (P < 0.05). The best cut-off values for BMI in the four stages were 23.47, 30.49, 26.04 and 25.47 kg/m2. The non-linear spline test at BMI in 42 days postpartum, current and MetS in lactation was statistically significant (P non-linear = 0.0223, 0.0003). The mediation effect of all chains have to work through lactation BMI. The total indirect effect accounted for 80.95% of the total effect. CONCLUSIONS: The risk of MetS in lactating women is due to a high BMI base before pregnancy and postpartum. High BMI in all stages of pregnancy and postpartum were risk factors for MetS in lactation. BMI during lactation plays a key role in the risk of MetS.

Enhancing Uranium Removal with a Titanium-Incorporated Zirconium-Based Metal-Organic Framework.

The urgent need to efficiently and rapidly decontaminate uranium contamination in aquatic environments underscores its significance for ecological preservation and environmental restoration. Herein, a series of titanium-doped zirconium-based metal-organic frameworks were meticulously synthesized through a stepwise process. The resultant hybrid bimetallic materials, denoted as NU-Zr-n%Ti, exhibited remarkable efficiency in eliminating uranium (U (VI)) from aqueous solution. Batch experiments were executed to comprehensively assess the adsorption capabilities of NU-Zr-n%Ti. Notably, the hybrid materials exhibited a substantial increase in adsorption capacity for U (VI) compared to the parent NU-1000 framework. Remarkably, the optimized NU-Zr-15%Ti displayed a noteworthy adsorption capacity (∼118 mg g-1) along with exceptionally rapid kinetics at pH 4.0, surpassing that of pristine NU-1000 by a factor of 10. This heightened selectivity for U (VI) persisted even when diverse ions exist. The dominant mechanisms driving this high adsorption capacity were identified as the robust electrostatic attraction between the negatively charged surface of NU-Zr-15%Ti and positively charged U (VI) species as well as surface complexation. Consequently, NU-Zr-15%Ti emerges as a promising contender for addressing uranium-laden wastewater treatment and disposal due to its favorable sequestration performance.

A Strategy for Studying Environmental Engineering: Simple Hydrothermal Synthesis of Flower-Shaped Stannous Sulfide Nanomaterials for Efficient Cataluminescence Sensing of Diethyl Ether.

In this work, flower-like stannous sulfide (SnS) nanomaterials are synthesized using a hydrothermal method and used as sensitive materials for cataluminescence (CTL)-based detection of diethyl ether. Gas sensors based on SnS nanomaterials are prepared, and the SnS nanomaterials exhibit excellent gas-sensitive behavior towards ether. High sensitivity to ether is achieved at a relatively low operating temperature (153 °C) compared to other common sensors. The response time is 3 s and the recovery time is 8 s. The CTL intensity shows a good linear relationship (R2 = 0.9931) with a detection limit of 0.15 ppm and the concentration of ether in the range of 1.5-60 ppm. The proposed CTL sensor shows good selectivity towards ether. In addition, a highly stable signal is obtained with a relative standard deviation of 1.5%. This study indicates that the SnS-based sensor has excellent gas-sensitive performance and shows potential for applications in the detection of ether.

Large-scale pathway reconstruction and colorimetric screening accelerate cellular metabolism engineering.

The capability to manipulate and analyze hard-wired metabolic pathways sets the pace at which we can engineer cellular metabolism. Here, we present a framework to extensively rewrite the central metabolic pathway for malonyl-CoA biosynthesis in yeast and readily assess malonyl-CoA output based on pathway-scale DNA reconstruction in combination with colorimetric screening (Pracs). We applied Pracs to generate and test millions of enzyme variants by introducing genetic mutations into the whole set of genes encoding the malonyl-CoA biosynthetic pathway and identified hundreds of beneficial enzyme mutants with increased malonyl-CoA output. Furthermore, the synthetic pathways reconstructed by randomly integrating these beneficial enzyme variants generated vast phenotypic diversity, with some displaying higher production of malonyl-CoA as well as other metabolites, such as carotenoids and betaxanthin, thus demonstrating the generic utility of Pracs to efficiently orchestrate central metabolism to optimize the production of different chemicals in various metabolic pathways. Pracs will be broadly useful to advance our ability to understand and engineer cellular metabolism.

Advanced inorganic lithium metasilicate binder for high-performance silicon anode.

Silicon (Si) is considered a high-capacity anode material with potential for next-generation lithium-ion batteries. However, the commercial application of Si anode is seriously hindered by huge volume variation (>300%) and limited Li+ diffusion ability. Herein, lithium metasilicate (LS), a novel inorganic binder, was innovatively developed to accommodate these challenges. Favorable compatibility is observed between the LS binder and Si nanoparticles (SiNPs) due to the existence of Si element within the LS skeleton. The interaction of the LS binder and SiNPs leads to a strong adhesion effect, enhancing the cycling stability of Si anode. The Si electrode with the LS binder presented an average discharge capacity of 2123 mAh/g at 0.84 A/g after 100 cycles. Furthermore, the presence of the Li+ transport channel within the LS binder enhances Li+ diffusion ability within Si anode. As a result, the average discharge capacity reaches 663 mAh/g at 8.4 A/g. This work thus explored new inorganic binder design approaches for Si anode, contributing to the advancement of high-performance Si anode.

Exposures to ambient air pollutants increase prevalence of sleep disorder in adults: Evidence from Wuhan Chronic Disease Cohort Study (WCDCS).

BACKGROUND: Sleep disorder contributes to memory dysfunction and chronic diseases. Clear evidence of environment disturbance, such as residential noise, are associated with an increased risk of sleep disorder. However, not enough studies have been conducted on association between residential air pollutants and sleep disorder. We sought to determine whether exposures to residential air pollutants associated with risk of sleep disorder among adults. METHODS: Using the dataset of the Wuhan Chronic Disease Cohort Study (WCDCS), we investigated the prevalence of sleep disorder and five sleep disorder symptoms in the study. The data of air pollutants (including PM10, PM2.5, NO2, SO2 and O3) were obtained from 10 air quality monitoring stations in Wuhan. We utilized logistic regression model to evaluate the associations of five types of air pollutants with odds ratio (OR) of sleep disorder and symptoms. The potential moderating effects of socio-demographic factors in the associations were explored using the interaction effects model. RESULTS: Of the study participants, 52.1 % had sleep disorder. Exposures to higher concentrations of air pollutants were associated with increased prevalence of sleep disorder. For example, per interquartile range (IQR) increases in concentrations of PM10, PM2.5 or SO2 corresponded to the increase of sleep disorder increased prevalence at 14.7 % (adjusted odds ratio (aOR) = 1.147, 95 %CI:1.062, 1.240), 8.9 % (aOR = 1.089, 95 %CI: 1.003, 1.182) and 15.8 % (aOR = 1.158, 95 %CI: 1.065, 1.260). For symptoms specific analyses, significant linkages of PM10, PM2.5, SO2 with difficulty in falling asleep, wake up after falling asleep and early awaken were observed. Moderating effects of age and place of residence on the linkages of PM10 with increased prevalence of sleep disorder were identified. CONCLUSION: Higher level of air pollution exposure could increase the prevalence of sleep disorder. Middle-aged and elderly population, as well as the rural residents are more likely to suffer from sleep disorder.

Independent and interactive associations between greenness and ambient pollutants on novel glycolipid metabolism biomarkers: A national repeated measurement study.

This study aims to investigate the independent and interactive effects of greenness and ambient pollutants on novel glycolipid metabolism biomarkers. A repeated national cohort study was conducted among 5085 adults from 150 counties/districts across China, with levels of novel glycolipid metabolism biomarkers of TyG index, TG/HDL-c, TC/HDL-c, and non-HDL-c measured. Exposure levels of greenness and ambient pollutants (including PM1, PM2.5, PM10, and NO2) for each participant were determined based on their residential location. Linear mixed-effect and interactive models were used to evaluate the independent and interactive effects between greenness and ambient pollutants on the four novel glycolipid metabolism biomarkers. In the main models, the changes [ß (95% CIs)] of TyG index, TG/HDL-c, TC/HDL-c, and non-HDL-c were -0.021 (-0.036, -0.007), -0.120 (-0.175, -0.066), -0.092 (-0.122, -0.062), and -0.445 (-1.370, 0.480) for every 0.1 increase in NDVI, and were 0.004 (0.003, 0.005), 0.014 (0.009, 0.019), 0.009 (0.006, 0.011), and 0.067 (-0.019, 0.154) for every 1 µg/m3 increase in PM1. Results of interactive analyses demonstrated that individuals living in low-polluted areas could get greater benefits from greenness than those living in highly-polluted areas. Additionally, the results of mediation analyses revealed that PM2.5 mediated 14.40% of the association between greenness and the TyG index. Further research is needed to validate our findings.

Evaluation of prevention and treatment effects of fibroblast growth factor-21 in BLM-induced pulmonary fibrosis.

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-ß and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis.

Network pharmacology and experimental studies for deciphering the molecular targets and mechanisms of Chaihu Shugan powder in the treatment of functional dyspepsia.

BACKGROUND: Chaihu Shugan powder (CSP) is a prevalent prescription product used in the treatment functional dyspepsia (FD) in China. However, the underlying pharmacological mechanisms involved in the treatment of FD remain unclear. OBJECTIVE: To explore the key components of CSP and their molecular targets and mechanisms in the treatment of FD. METHODS: Active compounds for CSP were identified from the TCMSP and SymMap databases, and the relevant targets were predicted. FD-related targets were obtained from the GeneCards and CTD database. In addition, using the protein-protein interactions (PPI) analysis, the common targets were obtained. Furthermore, the compound-target networks were created with Cytoscape. Finally, molecular docking was performed to identify the core targets and validate them experimentally. RESULTS: In total, 78 active compounds and 671 related targets of CSP were obtained. PPI network analysis identified 15 key FD-related compound targets. Molecular docking revealed that sitosterol and hyndarin exhibited good binding activities with AKT1 and IL6, respectively. Animal experiments have shown that CSP effectively increased the protein levels of AKT1 and reduced the serum levels of IL-6 in FD rats. CONCLUSION: This study provides a theoretical evidence for the analysis of the molecular targets and mechanisms of the action of CSP in FD.

A collaborative diffusion mechanism of multiple atoms during Cu-Ag bimetal surface reconstruction.

The reconstruction of bimetals under reaction conditions is critical for precisely controlling the catalytic performance of bimetallic catalysts. The surface diffusion mechanisms of Cu@Ag nanoparticles before and after CO adsorption were studied in this work. The diffusion patterns with the lowest energy barrier were determined by using ab initio molecular dynamics and meta-dynamics simulations. The effects of nanoparticle size, surface species and CO adsorption were taken into account. We present a mechanism of multiple atom collaborative diffusion during Cu@Ag bimetal reconstruction: surface atoms diffuse outward to form adatoms first, with nearby atoms occupying the original position of the outward diffused atom, and the outward diffusion can accelerate the inward diffusion of nearby surface atoms. The surface diffusion mechanisms of Cu@Ag under a CO atmosphere are different from those of Pd@Au that we previously presented, due to the different diffusion abilities of metal atoms. Our study provides a potential strategy to control the beginning of reconstruction to change the stability of bimetals under reaction conditions.

Clinical experience in laparoscopic treatment of gallbladder perforation.

Aim: We herein present our clinical experience in laparoscopic surgery for gallbladder perforation (GBP). Materials and Methods: Retrospective analysis was performed on the clinical data of 44 patients who diagnosed with GBP from January 2015 to November 2020. Results: The mean age of the 44 patients was 64.0 years and the female-to-male ratio was 20:24. The most common type of GBP was Type II, followed by Type I and Type III (31:9:4). 72.7% of the patients were diagnosed with GBP at the time of surgery. Laparoscopic surgery was performed for 38 (86.4%) patients, with a conversion rate of 13.2%. The mean length of hospital stays was 7.8 days. The mortality and morbidity rates were 2.3% and 11.4%, respectively. Conclusions: Pre-operative diagnosis of GBP is difficult. Laparoscopic surgery is safe, feasible and effective for patients with GBP.

Radiomic features from dynamic susceptibility contrast perfusion-weighted imaging improve the three-class prediction of molecular subtypes in patients with adult diffuse gliomas.

OBJECTIVES: To investigate whether radiomic features extracted from dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) can improve the prediction of the molecular subtypes of adult diffuse gliomas, and to further develop and validate a multimodal radiomic model by integrating radiomic features from conventional and perfusion MRI. METHODS: We extracted 1197 radiomic features from each sequence of conventional MRI and DSC-PWI, respectively. The Boruta algorithm was used for feature selection and combination, and a three-class random forest method was applied to construct the models. We also constructed a combined model by integrating radiomic features and clinical metrics. The models' diagnostic performance for discriminating the molecular subtypes (IDH wild type [IDHwt], IDH mutant and 1p/19q-noncodeleted [IDHmut-noncodel], and IDH mutant and 1p/19q-codeleted [IDHmut-codel]) was compared using AUCs in the validation set. RESULTS: We included 272 patients (training set, n = 166; validation set, n = 106) with grade II-IV gliomas (mean age, 48.7 years; range, 19-77 years). The proportions of the molecular subtypes were 66.2% IDHwt, 15.1% IDHmut-noncodel, and 18.8% IDHmut-codel. Nineteen radiomic features (13 from conventional MRI and 6 from DSC-PWI) were selected to build the multimodal radiomic model. In the validation set, the multimodal radiomic model showed better performance than the conventional radiomic model did in predicting the IDHwt and IDHmut-codel subtypes, which was comparable to the conventional radiomic model in predicting the IDHmut-noncodel subtype. The multimodal radiomic model yielded similar performance as the combined model in predicting the three molecular subtypes. CONCLUSIONS: Adding DSC-PWI to conventional MRI can improve molecular subtype prediction in patients with diffuse gliomas. KEY POINTS: • The multimodal radiomic model outperformed conventional MRI when predicting both the IDH wild type and IDH mutant and 1p/19q-codeleted subtypes of gliomas. • The multimodal radiomic model showed comparable performance to the combined model in the prediction of the three molecular subtypes. • Radiomic features from T1-weighted gadolinium contrast-enhanced and relative cerebral blood volume images played an important role in the prediction of molecular subtypes.

Intratympanic microcrystals of dexamethasone and lipoic acid for the treatment of cisplatin-induced inner ear injury.

Steroids (anti-inflammatory drugs) combined with antioxidants are frequently prescribed to treat cisplatin (CP)-induced hearing loss in the clinic. Compared to systemic administration of free drugs, local drug delivery systems offer better therapeutic qualities and patient compliance since they not only can bypass the blood-labyrinth barrier but also can perform sustained release. In this work, dexamethasone (DEX) and lipoic acid (LA) non-spherical microcrystals (MCs) were prepared without complicated chemical modification. Following a series of physical characterizations, including morphology, stability and injectability, dissolution and round window membrane distribution of MCs, DEX MCs, LA MCs and the simple mixture of DEX MCs + LA MCs (combination group) were administered in guinea pigs by intratympanic injection. We found that LA MCs enabled improvement of DEX absorption in the combination group compared to a single dose. In addition, no significant morphological changes or inflammatory responses were observed in cochlear tissue, indicating good biocompatibility. Finally, the combination group also demonstrated synergistic therapeutic effect for protecting hair cells against CP-induced damage. The local co delivery of DEX MCs and LA MCs offers a new strategy for the treatment of CP-induced inner ear injury since they provide sustained anti-inflammatory and antioxidant effects simultaneously.