Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

New Indole Diketopiperazine Alkaloids from Soft Coral-Associated Epiphytic Fungus Aspergillus versicolor CGF 9-1-2.

Two new indole diketopiperazine alkaloids (IDAs), (+)19-epi-sclerotiamide (1) and (-)19-epi-sclerotiamide (2), along with 13 known analogs (3-15), were isolated from a soft coral-associated epiphytic fungus Aspergillus versicolor CGF 9-1-2. The structures of two new compounds were established based on the combination of HR-ESI-MS, 1D and 2D NMR spectroscopy, optical rotation measurements and quantum chemical 13 C-NMR, the absolute configurations were determined by experimental and electronic circular dichroism (ECD) calculations. The results of molecular docking showed that all the compounds had a good binding with TDP1, TDP2, TOP1, TOP2, Ache, NLRP3, EGFR, EGFR L858R, EGFR T790M and EGFR T790/L858. Biological evaluation of compounds 3, 6, 8, 11 showed that 3 exerted a strong inhibitory effect on TDP2 with a rate of 81.72 %.

Two new alkaloids produced by Dothideomycetes sp. BMC-101 isolated from the Magnolia grandiflora.

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

Photochromic Azobenzene Inverse Opal Film toward Dynamic Anti-Fake Pattern.

Azobenzene mesogens have garnered considerable research attention in the realm of photo-responsive materials due to their reversible trans-cis isomerization. In this paper, we demonstrate an azobenzene inverse opal film synthesized via photo-polymerization from a SiO2 opal template. The proposed design exhibits intriguing optical properties, including dynamic fluorescent features, distinct fluorescent enhancement, and an anti-fake micropattern with a switchable structure color. This work holds significant importance for advancing the development of novel optical devices.

Determination of Multiple Neurotransmitters through LC-MS/MS to Confirm the Therapeutic Effects of Althaea rosea Flower on TTX-Intoxicated Rats.

Tetrodotoxin (TTX) inhibits neurotransmission in animals, and there is no specific antidote. In clinical practice in China, Althaea rosea (A. rosea flower) extract has been used to treat TTX poisoning. In this work, the efficacy of the ethyl acetate fraction extract of A. rosea flower in treating TTX poisoning in rats was investigated. A high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine nine neurotransmitters in rat brain tissue, including γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), noradrenaline (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), epinephrine (E), and tyramine (Tyn). The detoxifying effect of A. rosea flower was verified by comparing the changes in neurotransmitters' content in brain tissue before and after poisoning in rats. The assay was performed in multiple reaction monitoring mode. The quantification method was performed by plotting an internal-standard working curve with good linearity (R2 > 0.9941) and sensitivity. Analyte recoveries were 94.04-107.53% (RSD < 4.21%). Results indicated that the levels of 5-HT, DA, E, and NE in the brains of TTX-intoxicated rats decreased, whereas the levels of GABA, Tyn, and 5-HIAA showed an opposite trend, and HVA and DOPAC were not detected. The levels of all seven neurotransmitters returned to normal after the gavage administration of ethyl acetate extract of A. rosea flower to prove that the ethyl acetate extract of A. rosea flower had a therapeutic effect on TTX poisoning. The work provided new ideas for studies on TTX detoxification.

Characterization and optimization of the LAC4 upstream region for low-leakage expression in Kluyveromyces marxianus.

Kluyveromyces marxianus is a promising host for the production of heterologous proteins, chemicals, and bioethanol. One superior feature of this species is its capacity to assimilate lactose, which is rendered by the LAC12-LAC4 gene pair encoding a lactose permease and a ß-galactosidase enzyme. Little is known about the regulation of LAC4 in K. marxianus. In this study, we showed the presence of weak glucose repression in the regulation of LAC4 and that might contribute to the leaky expression of LAC4 in the glucose medium. In a mutagenesis screen of 1000-bp LAC4 upstream region, one mutant region, named H1, drove low-leakage expression of a URA3 reporter gene in glucose medium. Two mutations inside a polyadenosine stretch (poly(A)) of 5' UTR were major contributors to the low-leakage phenotype of H1. H1 directed low-leakage expression of GFP on a plasmid and that of LAC4 in situ in the glucose medium, which was not due to the reduction of mRNA levels. Meanwhile, H1 did not affect the induction of GFP or LAC4 by lactose. Cre recombinase expressed by H1 caused lower toxicity in the repressive condition and achieved higher yield after induction, compared with that expressed by a wild-type LAC4 upstream region or a strong INU1 promoter. Our study suggested that poly(A) inside 5' UTR played a role in regulating the expression of LAC4 in the repressive condition. Meanwhile, H1 provided a base for the development of a strict inducible system for expressing industrial proteins, especially toxic proteins.

Adjuvant-free cellulose nanofiber vaccine induces permanent humoral immune response in mouse.

Vaccines have become one of the most effective strategies to deal with various infectious diseases and chronic noninfectious diseases, such as SARS virus, Novel Coronavirus, cancer, etc. However, recent studies have found that the neutralizing antibody titers induced by vaccines would drop to half level or even lower after vaccination. In this study, we designed a novel small-sized positively charged nanofiber-1 (PEI-CNF-1) as a vaccine carrier, which can induce a high long-term humoral immune response by controlled release of antigen. Further studies showed that PEI-CNF-1 could significantly induce the release of immune response factor IL-1ßand bone marrow-derived cell (BMDC) maturation. Moreover, compare to other cellulose nanofibers (CNFs), PEI-CNF-1 combined antigen (ovalbumin, OVA) induced and maintained the highest and longest antibody titers after vaccination. Interestingly, the antibody titers have no significant difference between at 21 and 90 d. Mechanically, we found that PEI-NCF-1 not only could control the slow-release of antigen, but also could be more easily swallowed by macrophages and metabolized by the bodies, thus presenting antigen more effectively. In conclusion, we believe that PEI-CNF-1 have a very high application prospect in inducing long-term humoral immune response, so as to achieve efficient prevention effect to epidemic viruses.

Direct Synthesis of Nanosheet-Stacked Hierarchical "Honey Stick-like" MFI Zeolites by an Aromatic Heterocyclic Dual-Functional Organic Structure-Directing Agent.

Soft template designing is the most promising strategy for the synthesis of zeolite nanosheets. MFI nanosheets directed by soft templates (containing long-chain alkyl groups or aromatic groups as hydrophobic component) can be found frequently; however, so far, MFI nanosheets synthesized by soft templates with aromatic heterocycle groups (e. g., s-triazine groups) are rare. Herein, a nanosheet-stacked hierarchical MFI zeolite (NSHM) has been synthesized by using a triply branched s-triazine-based surfactant as a bifunctional organic structure-directing agent. On the basis of a geometrical match relationship, a formation model has been proposed. Synthesized NSHM had abundant mesopores stacked by nanosheets and exhibited a high surface area (430 m2 ⋅ g-1 ). The 1 wt% Pd/NSHM attained a significant increase in yield of cyclohexanol/cyclohexanone mixture (from 66 to 85 %) in the oxidation of cyclohexane compared with Silicalite-1 and SBA-15 as supports.

The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis.

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 µM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 µM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Enhanced antitumor efficacy in colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon.

BACKGROUND: Tumor recurrence and metastasis occur at a high rate in patients with colon cancer. Identification of effective strategies for the treatment of colon cancer is critical. Recently, poly (lactic-co-glycolic acid) (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. We designed a dual-loaded nanoparticle drug delivery system to overcome the limitations of chemotherapeutic drugs used to treat colon cancer. METHODS: We developed epidermal growth factor (EGF) functionalized PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perfluorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for targeted treatment of colon cancer. CCK-8 assay, Hoechst33342 staining and flow cytometry were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Beside, animal experiment, histological analysis and immunofluorescence staining were adopted to further confirm the role of EGF-PLGA@5Fu/PFC NPs in vivo. RESULTS: The findings showed that EGF-PLGA@5Fu /PFC NPs had an average size 200 nm and a 5Fu-loading efficiency of 7.29%. Furthermore, in vitro release was pH-sensitive. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs into colon cancer cells. In addition, EGF-PLGA@5Fu/PFC NPs suppressed cell viability and induced apoptosis in SW620 cells to a greater extent than non-targeted NPs. In tumor xenografted mice, EGF-PLGA@5Fu/PFC NPs suppressed tumor growth more effectively than 5Fu, PLGA@5Fu or PLGA@5Fu/PFC NPs. Histopathological analysis further demonstrated that EGF-targeted NPs inhibited tumor growth to a greater extent than non-targeted or non-NP treatments. The improved therapeutic outcomes observed in this study were due to relief of tumor hypoxia by transport of oxygen by PFC to the tumors. CONCLUSION: We constructed a biocompatible nanodrug delivery system based on functionalized nanoparticles that provided a novel strategy for selective delivery of chemotherapy drugs to tumors.

Failure of enhanced recovery after surgery in laparoscopic colorectal surgery: a systematic review.

PURPOSE: Enhanced recovery after surgery programs has been applied extensively in laparoscopic colorectal surgery. However, several studies have found that some patients fail from ERAS programs. It is important to identify these patients so that remedial action can be taken in a timely manner. The aim of this study was to perform a systematic review of ERAS failure and related risk factors following laparoscopic colorectal surgery. METHODS: A literature search of the PubMed, EMBASE, OVID, and Cochrane databases was performed. The search strategy involved terms related to ERAS, failure, and colorectal surgery. The main outcomes were definitions of ERAS failure and related risk factors. RESULTS: Seven studies including 1463 patients were analyzed. The definition of ERAS failure was mostly associated with a prolonged postoperative length-of-stay (poLOS). Twenty-four kinds of identified risk factors were divided into three parts, the operative part, the pathophysiological part, and the ERAS elements, of which operative factors including more intraoperative blood loss and longer operative duration were the most frequently identified. CONCLUSIONS: ERAS failure was mostly related to a prolonged poLOS, and operative factors were the most frequently identified risk factors for ERAS failure following laparoscopic colorectal surgery. These findings will help physicians to take remedial action in a timely manner. Nonetheless, high-quality randomized controlled trials following a standardized framework for evaluating ERAS programs are needed in the future.

Three new methylated Δ8-pregnene steroids from the Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2.

Three new methylated Δ8-pregnene steroids, stemphylisteroids A-C (1-3) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. The absolute configuration of 1 was determined by X-ray crystallographic analysis. Compound 1 show antibacterial activity against Escherichia coli with the MIC value of 6.25 µg/mL, and 2 exhibited a broad spectrum of antibacterial activities against six pathogenic bacteria with the MIC values ranging from 12.5 to 50 µg/mL. The discovery of three methylated Δ8-pregnene steroids 1-3 are a further addition to diverse and complex array of methylated steroids.

Three-phase hollow fiber liquid-phase microextraction combined with HPLC for determination of three trace acidic plant growth regulators in Anoectochilus roxburghii (Wall.) Lindl.

The analysis of plant growth regulators presents a challenge due to their trace quantities and complex matrices. A novel, simple, and effective analytical method for the determination of three trace acidic plant growth regulators in Anoectochilus roxburghii (Wall.) Lindl was developed to address this issue. Three-phase hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography was applied for the enrichment, purification, and determination of three acidic plant growth regulators, namely, indole-3-acetic-acid, indole-3-butyric-acid, and (+)-abscisic acid. The factors affecting extraction performance, including extractant species, pH of donor and acceptor phases, salt addition dosage, extraction time, temperature, and stirring rate, were investigated and optimized. Under optimum conditions, the proposed method provided good linearity (R2 , 0.9994-0.9999), low limit of detection (0.038-0.12 ng/mL), and acceptable relative recoveries (56.7-117.6%). The enrichment factors were between 153 and 328. The developed method was successfully applied to the enrichment and determination of plant growth regulators in Anoectochilus roxburghii (Wall.) Lindl and exhibited increased purification capacity, higher sensitivity, and decreased organic solvent consumption compared with conventional sample preparation methods. This method may provide a testing platform for the monitoring of plant growth regulator residues, ensuring the safe and effective use of traditional Chinese medicine.

Very Short-Term Surface Solar Irradiance Forecasting Based On FengYun-4 Geostationary Satellite.

An algorithm to forecast very short-term (30-180 min) surface solar irradiance using visible and near infrared channels (AGRI) onboard the FengYun-4A (FY-4A) geostationary satellite was constructed and evaluated in this study. The forecasting products include global horizontal irradiance (GHI) and direct normal irradiance (DNI). The forecast results were validated using data from Chengde Meteorological Observatory for four typical months (October 2018, and January, April, and July 2019), representing the four seasons. Particle Image Velocimetry (PIV) was employed to calculate the cloud motion vector (CMV) field from the satellite images. The forecast results were compared with the smart persistence (SP) model. A seasonal study showed that July and April forecasting is more difficult than during October and January. For GHI forecasting, the algorithm outperformed the SP model for all forecasting horizons and all seasons, with the best result being produced in October; the skill score was greater than 20%. For DNI, the algorithm outperformed the SP model in July and October, with skill scores of about 12% and 11%, respectively. Annual performances were evaluated; the results show that the normalized root mean square error (nRMSE) value of GHI for 30-180 min horizon ranged from 26.78% to 36.84%, the skill score reached a maximum of 20.44% at the 30-min horizon, and the skill scores were all above 0 for all time horizons. For DNI, the maximum skill score was 6.62% at the 180-min horizon. Overall, compared with the SP model, the proposed algorithm is more accurate and reliable for GHI forecasting and slightly better for DNI forecasting.

[FOXO4 maintains senescence in human umbilical cord mesenchymal stem cells by repressing apoptosis].

The purpose of the present study was to investigate the effects of forkhead box O4 (FOXO4) on the senescence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSCs were induced to senescence by natural passage, and FOXO4 expression was inhibited by lentiviral shRNA transfection. The hallmark of cell senescence was analyzed by ß-galactosidase staining, and the cell viability was assayed by CCK-8 method. Flow cytometry was used to investigate the apoptosis of hUC-MSCs. The expression levels of Bcl-2, Bax, FOXO4, interleukin 6 (IL-6) and cleaved Caspase-3 were detected by qPCR and Western blot. Immunofluorescence staining was used to detect FOXO4 expression. The amount of IL-6 secreted by hUC-MSCs was detected by ELISA. The results showed that, compared with the passage 1, senescent hUC-MSCs showed up-regulated expression levels of Bax and FOXO4, down-regulated expression levels of Bcl-2 and cleaved Caspase-3, and increased IL-6 mRNA expression and secretion. FOXO4 inhibition in senescent hUC-MSCs promoted cell apoptosis, reduced cell viability, and inhibited the mRNA expression and secretion of IL-6. These results suggest that FOXO4 maintains viability and function of senescent hUC-MSCs by repressing their apoptosis response, thus accelerating senescence of the whole cell colony.

Upregulation of long noncoding RNA TUG1 contributes to the development of laryngocarcinoma by targeting miR-145-5p/ROCK1 axis.

Laryngocarcinoma is the most common head and neck cancer and has a high incidence and mortality, causing about 83 000 deaths per year worldwide. Our research aimed to investigate the possible role of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in laryngocarcinoma development. The messenger RNA (mRNA) levels of TUG1 in tumor tissues and control (plasma) samples of laryngocarcinoma patients as well as in laryngocarcinoma cells were detected. The influences of TUG1 suppression on cell biological processes (viability, apoptosis, migration, and invasion) and cytoskeleton rearrangement in laryngocarcinoma cells were tested. Moreover, we investigated the regulatory interaction between TUG1 and miR-145-5p, and identified the target gene of miR-145-5p. The association between TUG1 and the protein expressions of RhoA/rho associated coiled-coil containing protein kinase (ROCK)/matrix metalloproteinases (MMPs) pathway-associated factors were detected. TUG1 was found to be highly expressed in tumor tissues and plasma samples of laryngocarcinoma patients as well as in laryngocarcinoma cells. Suppression of TUG1 decreased laryngocarcinoma cell viability, increased apoptosis, and suppression migration, invasion, and cytoskeleton rearrangement. Moreover, TUG1 negatively regulated miR-145-5p. TUG1 regulated tumor growth (viability and apoptosis) and metastasis through miR-145-5p. Furthermore, ROCK1 was targeted by miR-145-5p, and miR-145-5p/ROCK1 partner was involved in the process of tumor growth and metastasis. Finally, we found that TUG1 functioned on laryngocarcinoma by activating RhoA/ROCK/MMPs pathway. Our study reveals that lncRNA TUG1 is upregulated in laryngocarcinoma and may be involved in the process of laryngocarcinoma through miR-145-5p downregulation and activating the RhoA/ROCK/MMPs signals.

Overexpression of miR-301a-3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer-1 and runt-related transcription factor 3.

Colorectal cancer (CRC) is the third most common type of cancer. MicroRNAs have been reported to participate in the progression of various cancers. In previous studies, miR-301a-3p expression was shown to be upregulated in CRC tissues. However, the underlying mechanism of miR-301a-3p in CRC has not yet been elucidated. Herein, the level of miR-301a-3p was found to be significantly upregulated in CRC clinical tissues and cell lines (HT29 and SW620). In addition, overexpression of miR-301a-3p obviously promoted cell proliferation, migration and invasion, and inhibited cell apoptosis in CRC cells. Meanwhile, upregulated miR-301a-3p expression also enhanced the expressions of Bax, caspase-3, caspase-9, matrix metalloproteinase (MMP)-2, and MMP-9, while the expression of Bax-2 was decreased. Furthermore, deleted in liver cancer-1 (DLC-1) and runt-related transcription factor 3 (RUNX3) were verified to be direct target genes of miR-301a-3p. Furthermore, overexpression of DLC-1 and RUNX3 revealed antitumor effects in CRC cell lines with the inhibition of cell proliferation, migration and invasion, and the induction of cell apoptosis. In addition, the expressions of Bax, caspase-3, caspase-3, MMP-2, and MMP-9 could be decreased after upregulating the expressions of DLC-1 and RUNX3, along with the upregulation of Bax-2. Moreover, overexpression of miR-301a-3p could promote the growth of xenograft tumors and liver metastasis in vivo, along with reducing the expressions of DLC-1 and RUNX3. Overall, miR-301a-3p might act as a tumor inducer in CRC cells through negatively regulating DLC-1 and RUNX3.

Relatively slow stochastic gene-state switching in the presence of positive feedback significantly broadens the region of bimodality through stabilizing the uninduced phenotypic state.

Within an isogenic population, even in the same extracellular environment, individual cells can exhibit various phenotypic states. The exact role of stochastic gene-state switching regulating the transition among these phenotypic states in a single cell is not fully understood, especially in the presence of positive feedback. Recent high-precision single-cell measurements showed that, at least in bacteria, switching in gene states is slow relative to the typical rates of active transcription and translation. Hence using the lac operon as an archetype, in such a region of operon-state switching, we present a fluctuating-rate model for this classical gene regulation module, incorporating the more realistic operon-state switching mechanism that was recently elucidated. We found that the positive feedback mechanism induces bistability (referred to as deterministic bistability), and that the parameter range for its occurrence is significantly broadened by stochastic operon-state switching. We further show that in the absence of positive feedback, operon-state switching must be extremely slow to trigger bistability by itself. However, in the presence of positive feedback, which stabilizes the induced state, the relatively slow operon-state switching kinetics within the physiological region are sufficient to stabilize the uninduced state, together generating a broadened parameter region of bistability (referred to as stochastic bistability). We illustrate the opposite phenotype-transition rate dependence upon the operon-state switching rates in the two types of bistability, with the aid of a recently proposed rate formula for fluctuating-rate models. The rate formula also predicts a maximal transition rate in the intermediate region of operon-state switching, which is validated by numerical simulations in our model. Overall, our findings suggest a biological function of transcriptional "variations" among genetically identical cells, for the emergence of bistability and transition between phenotypic states.

Can amide proton transfer-weighted imaging differentiate tumor grade and predict Ki-67 proliferation status of meningioma?

OBJECTIVES: To determine the utility of the amide proton transfer-weighted MR imaging in differentiating the WHO grade and predict proliferative activity of meningioma. METHODS: Fifty-three patients with WHO grade I meningiomas and 26 patients with WHO grade II meningiomas underwent conventional and APT-weighted sequences on a 3.0 Tesla MR before clinical intervention. The APT-weighted (APTw) parameters in the solid tumor region were obtained and compared between two grades using the t test; the receiver operating characteristic (ROC) curve was used to assess the best parameter for predicting the grade of meningiomas. Pearson's correlation coefficient was calculated between the APTwmax and Ki-67 labeling index in meningiomas. RESULTS: The APTwmax and APTwmean values were not significantly different between WHO grade I and grade II meningiomas (p = 0.103 and p = 0.318). The APTwmin value was higher and the APTwmax-min value was lower in WHO grade II meningiomas than in WHO grade I tumors (p = 0.027 and p = 0.019). But the APTwmin was higher and the APTwmax-min was lower in microcystic meningiomas than in WHO grade II meningiomas (p = 0.001 and p = 0.006). The APTwmin combined with APTwmax-min showed the best diagnostic performance in predicting the grade of meningiomas with an AUC of 0.772. The APTwmax value was positively correlated with Ki-67 labeling index (r = 0.817, p < 0.001) in meningiomas; the regression equation for the Ki-67 labeling index (%) (Y) and APTwmax (%) (X) was Y = 4.9 × X - 12.4 (R2 = 0.667, p < 0.001). CONCLUSION: As a noninvasive imaging method, the ability of APTw-MR imaging in differentiating the grade of meningiomas is limited, but the technology can be used to predict the proliferative activity of meningioma. KEY POINTS: • The APTw min value was higher and the APTw max-min value was lower in WHO grade II meningioma than in grade I tumors. • The APTw min value was higher and the APTw max-min value was lower in microcystic meningiomas than in WHO grade II meningiomas. • The APTw max value was positively correlated with meningioma proliferation index.