Enhancing Concrete Mechanical Properties through Basalt Fibers and Calcium Sulfate Whiskers: Optimizing Compressive Strength, Elasticity, and Pore Structure.

To study the effects of basalt fibers (BFs), calcium sulfate whiskers (CSWs), and modified calcium sulfate whiskers (MCSWs) on the compressive strength and dynamic modulus of elasticity of concrete, this paper utilizes Mercury Intrusion Porosimetry (MIP) to measure the microstructure of concrete and calculate the fractal dimension of pore surface area. The results indicate that both CSWs and BFs can increase the compressive strength of concrete. CSWs can enhance the dynamic modulus of elasticity of concrete, while the effect of BFs on the dynamic modulus of elasticity is not significant. The improvement in compressive strength and dynamic modulus of elasticity provided by MCSWs is significantly greater than that provided by CSWs. Both CSWs and BFs can effectively improve the pore structure of concrete and have a significant impact on the surface fractal dimension. CSWs inhibit the formation of ink-bottle pores, while BFs increase the number of ink-bottle pores. Due to the ink-bottle pore effect, the fractal dimension of the capillary pore surface is generally greater than three, lacking fractal characteristics. The compressive strength and dynamic modulus of elasticity of concrete have a good correlation with the fractal dimensions of large pores and transition pores.

A progress update on the biological effects of biodegradable microplastics on soil and ocean environment: A perfect substitute or new threat?

Conventional plastics are inherently difficult to degrade, causing serious plastic pollution. With the development of society, biodegradable plastics (BPs) are considered as an alternative to traditional plastics. However, current research indicated that BPs do not undergo complete degradation in natural environments. Instead, they may convert into biodegradable microplastics (BMPs) at an accelerated rate, thereby posing a significant threat to environment. In this paper, the definition, application, distribution, degradation behaviors, bioaccumulation and biomagnification of BPs were reviewed. And the impacts of BMPs on soil and marine ecosystems, in terms of physicochemical property, nutrient cycling, microorganisms, plants and animals were comprehensively summarized. The effects of combined exposure of BMPs with other pollutants, and the mechanism of ecotoxicity induced by BMPs were also addressed. It was found that BMPs reduced pH, increased DOC content, and disrupted the nitrification of nitrogen cycle in soil ecosystem. The shoot dry weight, pod number and root growth of soil plants, and reproduction and body length of soil animals were inhibited by BMPs. Furthermore, the growth of marine plants, and locomotion, body length and survival of marine animals were suppressed by BMPs. Additionally, the ecotoxicity of combined exposure of BMPs with other pollutants has not been uniformly concluded. Exposure to BMPs induced several types of toxicity, including neurotoxicity, gastrointestinal toxicity, reproductive toxicity, immunotoxicity and genotoxicity. The future calls for heightened attention towards the regulation of the degradation of BPs in the environment, and pursuit of interventions aimed at mitigating their ecotoxicity and potential health risks to human.

Molecular Characterization of Plant Volatile Compound Interactions with Cnaphalocrocis medinalis Odorant-Binding Proteins.

Odorant-binding proteins (OBPs) play important roles in the insect olfactory system since they bind external odor molecules to trigger insect olfactory responses. Previous studies have identified some plant-derived volatiles that attract the pervasive insect pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), such as phenylacetaldehyde, benzyl acetate, 1-heptanol, and hexanal. To characterize the roles of CmedOBPs in the recognition of these four volatiles, we analyzed the binding abilities of selected CmedOBPs to each of the four compounds, as well as the expression patterns of CmedOBPs in different developmental stages of C. medinalis adult. Antennaes of C. medinalis adults were sensitive to the studied plant volatile combinations. Expression levels of multiple CmedOBPs were significantly increased in the antennae of 2-day-old adults after exposure to volatiles. CmedOBP1, CmedOBP6, CmedPBP1, CmedPBP2, and CmedGOBP2 were significantly up-regulated in the antennae of volatile-stimulated female and male adults when compared to untreated controls. Fluorescence competition assays confirmed that CmedOBP1 could strongly bind 1-heptanol, hexanal, and phenylacetaldehyde; CmedOBP15 strongly bound benzyl acetate and phenylacetaldehyde; and CmedOBP26 could weakly bind 1-heptanol. This study lays a theoretical foundation for further analysis of the mechanisms by which plant volatiles can attract C. medinalis. It also provides a technical basis for the future development of efficient plant volatile attractants of C. medinalis.

Reversible Multimode Luminescence Modulations in Photochromic-Translucent Yb3+/Eu3+ Codoped K0.5Na0.5NbO3 Ceramics.

Luminescent tunable materials have promising application potential in optical switches, optical information storage, and so on. Although europium (Eu) is a good downconversion red luminescent rare earth element, there are few studies on the upconversion luminescence and photochromism of Eu-doped potassium sodium niobate (KNN) ferroelectrics. In this paper, Eu3+ and Yb3+ codoped KNN translucent ferroelectric ceramics were synthesized and the effect of Yb3+ content on the luminescence and photochromism is studied. Both the up- and downconversion luminescence intensity and decay rate before and after photochromism can be well controlled by Yb3+ content. That is, an upconversion luminescent translucent ceramic that can be completely discolored by 405 nm light illumination for 10 s was obtained. The luminescence modulations are closely related to the evolution of oxygen vacancy and crystal field around the luminescence center, which can be verified by the illumination-induced electron paramagnetic resonance (EPR) signal and local piezoresponse switching behavior variation as well as the discovery of energy level splitting and spectral line shift. We believe that this work shows a paradigm for designing high-performance reversible multimode luminescence modulation ferroelectric ceramics.

Development of a Prognostic Nomogram for Modified Tinnitus Relieving Sound Therapy for Subjective Tinnitus.

OBJECTIVE: We aimed to develop a modified tinnitus-relieving sound system and establish a model for predicting its treatment effects. STUDY DESIGN: Retrospective study. SETTING: Tinnitus Specialist Clinic of Eye & ENT Hospital, Fudan University. METHODS: We recruited 107 patients undergoing modified tinnitus-relieving sounds between August 2020 and May 2021. Patients were divided into training (n = 75) and validation (n = 32) cohorts in a 7:3 ratio. The treatment outcome was Tinnitus Handicapped Inventory scores. Features were established using a least absolute shrinkage and selection operator-derived logistic regression model, where the selected clinical risk factors were included in the multivariate logistic regression, and a nomogram was established based on the model. The discrimination and calibration abilities of the nomogram were evaluated using the Hosmer-Lemeshow test and calibration curves. Decision curve analysis (DCA) was used to evaluate the net benefit of predictive efficacy. RESULTS: Multivariate logistic analysis indicated that the initial Tinnitus Handicapped Inventory score (odds ratio [OR]: 1.13 [1.07-1.19], P < .001) and treatment duration (OR: 3.4 [1.34-8.62], P < .001) were positive factors for improved tinnitus. The nomogram model that included baseline Tinnitus Handicapped Inventory score and treatment duration achieved a better concordance index of 0.880. DCA revealed that the nomogram model could lead to net benefits and exhibited a wider range of threshold probabilities for the prediction of therapeutic effects. CONCLUSION: Our study suggests that the nomogram model, including baseline Tinnitus Handicapped Inventory score and treatment duration, could achieve optimal performance in the preoperative prediction of the therapeutic effect of modified tinnitus-relieving sound.

Deep learning-based prediction for time-dependent chloride penetration in concrete exposed to coastal environment.

The application of deep learning methods in civil engineering has gained significant attention, but its usage in studying chloride penetration in concrete is still in its early stages. This research paper focuses on predicting and analyzing chloride profiles using deep learning methods based on measured data from concrete exposed for 600 days in a coastal environment. The study reveals that Bidirectional Long Short-Term Memory (Bi-LSTM) and Convolutional Neural Network (CNN) models exhibit rapid convergence during the training stage, but fail to achieve satisfactory accuracy when predicting chloride profiles. Additionally, the Gate Recurrent Unit (GRU) model proves to be more efficient than the Long Short-Term Memory (LSTM) model, but its prediction accuracy falls short compared to LSTM for further predictions. However, by optimizing the LSTM model through parameters such as the dropout layer, hidden units, iteration times, and initial learning rate, significant improvements are achieved. The mean absolute error (MAE), determinable coefficient (R2), root mean square error (RMSE), and mean absolute percentage error (MAPE) values are reported as 0.0271, 0.9752, 0.0357, and 5.41%, respectively. Furthermore, the study successfully predicts desirable chloride profiles of concrete specimens at 720 days using the optimized LSTM model.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

BACKGROUND: Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry. METHODS: Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency. RESULTS: The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites). CONCLUSIONS: The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

An Accurate and Individualized Preoperative Estimation Method for the Linear Insertion Depth of Cochlear Implant Electrode Arrays Based on Computed Tomography.

OBJECTIVES: Cochlear implantation or auditory brainstem implantation is currently the only accepted method for improving severe or profound sensorineural hearing loss. The length of the electrodes implanted during cochlear implantation is closely related to the degree of hearing improvement of hearing after the surgery. We aimed to explore new methods to accurately estimate the electrode array (EA) linear insertion depth based on computed tomography (CT) images prior surgery, which could help surgeons select the appropriate EA length for each patient. DESIGN: Previous studies estimated the linear insertion depth by measuring the length of the lateral wall of the cochlea rather than the electrode's path in the cochlea duct. Here, we determined the actual position of the EA on the CT image after cochlear surgery in order to predict the path of the EA, and the length of the predicted EA path was measured by the contouring technique (CoT) to estimate the linear insertion depth of the EA. Because CoT can only measure the length of the estimated EA path on a two-dimensional plane, we further modified the measurement by weighting the height of the cochlea and the length of the EA tail (the length of the last stimulating electrode to the end, which cannot be displayed on the CT image), which we termed the modified CoT + height + tail (MCHT) measurement. RESULTS: Based on our established method, MCHT could reduce the error to the submillimeter range (0.67 ± 0.37 mm) when estimating the linear insertion depth of various kinds of EAs compared with the actual implant length. The correlation coefficient between the linear insertion depth as predicted by MCHT and the actual was 0.958. The linear insertion depth estimated by this method was more accurate than that estimated using the classical CoT technique ( R = 0.442) and using the modified Escudé's method ( R = 0.585). CONCLUSIONS: MCHT is a method based on CT images that can accurately predict the linear insertion depth of cochlear implants preoperatively. This is the first report that we are aware of a method for predicting linear insertion depth before cochlear implantation with only submillimeter errors and that is tailored to different types of EAs.

[Imaging study of anatomical parameters related to pterygoid canal neurotomy].

Objective:Measuring the important anatomic parameters related to vidian neurectomy to locate the vidian nerve accurately and prevent the surgical complications. Methods:High resolution CT（HRCT） was used to measure the distance parameters between the important anatomic landmarks in 50 patients （100 sides） with chronic rhinosinusitis, sinus cyst or allergic rhinitis et al. The distance from the posterior opening of the palatovaginal canal to the upper edge of the sphenoidal process of palatine bone, the upper edge of the sphenoidal process of palatine bone to the external opening of the vidian canal, the external opening of the vidian canal to the greater palatine canal, and the external opening of the vidian canal to the foramen rotundus were measured. Results:The posterior opening of the palatovaginal canal, the upper edge of the sphenoidal process of palatine bone, the external opening of the vidian canal, the greater palatine canal, and the foramen rotundum are of great value in locating vidain nerve and preventing surgical complications. The distance from the posterior opening of the palatovaginal canal to the upper edge of the sphenoidal process of palatine bone, the upper edge of the sphenoidal process of palatine bone to the external opening of the vidian canal, the external opening of the vidian canal to the greater palatine canal, and the external opening of the vidian canal to the foramen rotundus were（12.46±1.19） mm, （3.23±0.36） mm, （6.09±0.75） mm and（7.6±1.16） mm respectively. Conclusion:HRCT can be used as a powerful tool for preoperative localization of the external pterygoid nerve orifice and its related important anatomical landmarks, and the preoperative distance parameters obtained are valuable for intraoperative localization of the pterygoid nerve to prevent the occurrence of complications.

Adaptive Cross Entropy for ultrasmall object detection in Computed Tomography with noisy labels.

Conventional size object detection has been extensively studied, whereas researches concerning ultrasmall object detection are rare due to lack of dataset. Here, considering that the stapes in the ear is the smallest bone in our body, we have collected the largest stapedial otosclerosis detection dataset from 633 stapedial otosclerosis patients and 269 normal cases to promote this direction. Nevertheless, noisy classification labels in our dataset are inevitable due to various subjective and objective factors, and this situation prevails in various fields. In this paper, we propose a novel and general noise tolerant loss function named Adaptive Cross Entropy (ACE) which needs no fine-tuning of hyperparameters for training with noisy labels. We provide both theoretical and empirical analyses for the proposed ACE loss and demonstrate its effectiveness in multiple public datasets. Besides, we find high-resolution representations crucial for ultrasmall object detection and present an auxiliary backbone called W-Net to address it accordingly. Extensive experiments demonstrate that the proposed ACE loss is able to boost the diagnosis performance under noisy label setting by a large margin. Furthermore, our W-Net can help extract sufficient high-resolution representations specialized for ultrasmall objects and achieve even better results. Hopefully, our work could provide more clues for future research on ultrasmall object detection and learning with noisy labels.

Development and evaluation of a new test kit for determination of immunosuppressants in blood by UHPLC-MS/MS.

In this study, we have developed and validated a new test kit that applied pure solvents instead of blood samples for determination of immunosuppressant drugs in blood by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). We have used commercially available quality control samples to verify this new test kit, and the results showed that the performance of our new kit was comparable with commercially available kits by immunoassays. The new test kit is pure solvent-based, which saves the cost and can be directly loaded without pre-treatment, thus shortening the detection time. The agreement between pure solvent-based kit and blood-based kit was also evaluated by Bland-Altman plot and two-tailed Student's T-test. For 97.08% of the 137 Tacrolimus clinical samples, the concentration difference between these two kits was laid within 20% of the mean concentration. The concentrations of 12 cyclosporine samples and 15 sirolimus samples obtained by both kits showed no significant difference evaluated by the two-tailed Student's T-test. These results further demonstrated the good agreement between these two types of test kits. Meanwhile, our pure solvent-based test kit could be stored stably for 14 weeks at -30 °C. Therefore, the newly developed pure solvent-based test kit can be used for detecting the whole blood immunosuppressant concentration and therapeutic drug monitoring of immunosuppressants.

Far-Red Light Triggered Production of Bispecific T Cell Engagers (BiTEs) from Engineered Cells for Antitumor Application.

Bispecific T-cell engagers (BiTEs), which have shown potent antitumor activity in humans, are emerging as one of the most promising immunotherapeutic strategies for cancer treatment in recent years. However, the clinical application of BiTEs nowadays has been hampered by their short half-life in the circulatory system due to their low molecular weight and rapid renal clearance. Inevitable continuous infusion of BiTEs has become a routine operation in order to achieve effective treatment, although it is costly, inconvenient, time-consuming, and even painful for patients in some cases. To develop an on-demand, tunable, and reversible approach to overcome these limitations, we assembled a transcription-control device into mammalian cells based on a bacterial far-red light (FRL) responsive signaling pathway to drive the expression of a BiTE against Glypican 3 (GPC3), which is a highly tumor-specific antigen expressed in most hepatocellular carcinomas (HCC). As demonstrated in in vitro experiments, we proved that the FRL sensitive device spatiotemporally responded to the control of FRL illumination and produced a therapeutic level of BiTEs that recruited and activated human T cells to eliminate GPC3 positive tumor cells. By functionally harnessing the power of optogenetics to remotely regulate the production of BiTEs from bioengineered cells and demonstrating its effectiveness in treating tumor cells, this study provides a novel approach to achieve an in vivo supply of BiTEs, which could be potentially applied to other formats of bispecific antibodies and facilitate their clinical applications.

An Iris Tumor Secondary to Talaromyces Marneffei Infection in a Patient with AIDS and Syphilis.

PURPOSE: To report a case of iris tumor secondary to Talaromyces marneffei infection in a patient with AIDS and syphilis. CASE REPORT: A 25-year-old man presented with gradual vision decrease in the right eye for 2 months. Ocular examination revealed best-corrected visual acuity (BCVA) of 0.12 and a vascularized and solid tumor at inferotemporal iris base in the right eye. There were some papulonecrotic skin lesions. Both serum treponema pallidum particle agglutination and human immunodeficiency virus antibody were positive. Non-target metagenome next-generation sequencing detected Talaromyces marneffei in the skin lesion and aqueous humor. After 8 weeks of oral voriconazole and fluconazole eyedrop treatment, the iris tumor completely subsided, and the BCVA improved to 1.0. CONCLUSION: Talaromyces marneffei infection may present as an iris tumor. Metagenome next-generation sequencing is helpful in diagnosis. Oral and topical anti-fungus therapy was sufficient to regress the disease without intraocular injection.

Magnetic resonance imaging investigations reveal that PM2.5 exposure triggers visual dysfunction in mice.

OBJECTIVES: To investigate how PM2.5 exposure affects the microstructure, metabolites or functions of the visual system. METHODS: C57BL/6J mice were randomly assigned to groups exposed to the filtered air (the control group) or the concentrated ambient PM2.5 (the PM2.5 group). Visual evoked potentials (VEP), electroretinograms (ERG), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and resting-state functional MRI (rsfMRI) were performed. Parameters were obtained and compared between the two groups, including latencies and amplitudes of the P1 wave, N1 wave and P2 wave from VEP, latencies and amplitudes of the a wave and b wave from ERG, fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) from DTI, visual cortex (VC) metabolites from 1H-MRS, and regional homogeneity (ReHo) from rsfMRI. RESULTS: Compared with the values of the control group, the PM2.5 group showed a prolonged N1 latency (43.11 ±â€¯7.94 ms vs. 38.75 ±â€¯4.60 ms) and lowered P1 amplitude (5.62 ±â€¯4.38 µV vs. 8.56 ±â€¯5.92 µV) on VEP (all p < 0.05). On ERG, the amplitude of the a wave was lowered (- 91.39 ±â€¯56.29 µV vs. - 138.68 ±â€¯89.05 µV), the amplitude of the b wave was lowered (194.38 ±â€¯126.27 µV vs. 284.72 ±â€¯170.99 µV), and the latency of the b wave was prolonged (37.78 ±â€¯10.72 ms vs. 33.01 ±â€¯4.34 ms) than the values of the control group (all p < 0.05). DTI indicated FA increase in the bilateral piriform cortex (Pir), FA decrease in the bilateral somatosensory cortex (S) and the bilateral striatum (Stri), AD decrease in the bilateral VC, the right S and the bilateral Pir, MD decrease in the bilateral Pir, and RD decrease in the bilateral Pir in the PM2.5 mice (all p < 0.05, Alphasim corrected). 1H-MRS showed Glutamate (Glu) increase and Phosphocholine (PCh) increase in the VC of the PM2.5 group than those of the control group (PCh 1.63 ±â€¯0.25 vs. 1.50 ±â€¯0.25; PCh/total creatine(tCr) 0.19 ±â€¯0.03 vs. 0.18 ±â€¯0.03; Glu 10.46 ±â€¯1.50 vs. 9.60 ±â€¯1.19; Glu/tcr 1.23 ±â€¯0.11 vs. 1.12 ±â€¯0.11) (all p < 0.05). rsfMRI showed higher ReHo in the PM2.5 mice in the left superior colliculus, the left motor cortex, the hippocampus, the periaqueductal gray and the right mesencephalic reticular formation (all p < 0.01, AlphaSim corrected). CONCLUSIONS: This study revealed that PM2.5 exposure triggered visual dysfunction, and altered microstructure, metabolite and function in the retina and visual brain areas along the visual system.

The use of explainable artificial intelligence to explore types of fenestral otosclerosis misdiagnosed when using temporal bone high-resolution computed tomography.

BACKGROUND: The purpose of this study was to explore the common characteristics of fenestral otosclerosis (OS) which are misdiagnosed, and develop a deep learning model for the diagnosis of fenestral OS based on temporal bone high-resolution computed tomography scans. METHODS: We conducted a study to explicitly analyze the clinical performance of otolaryngologists in diagnosing fenestral OS and developed an explainable deep learning model using 134,574 temporal bone high-resolution computed tomography (HRCT) slices collected from 1,294 patients for the automatic diagnosis of fenestral OS. We prospectively created an external test set with 31,774 CT slices from 144 patients, which contained 86 fenestral OS ears and 202 normal ears and used it to evaluate the performance of our otosclerosis-Logical Neural Network (LNN) model to assess its potential clinical utility. In addition, we compared the diagnostic acumen of seven otolaryngologists with the otosclerosis-LNN approach in the clinical test set, which was mixed with 78 fenestral OS and 62 normal ears. Finally, to evaluate the assisting value of the model, the seven participants were again invited to classify all cases in the clinical test set after referring to the diagnostic results of the model, to which they were blinded. RESULTS: The diagnostic performance of otologists was not satisfactory, and those CT samples which were misdiagnosed had similar characteristics. Based on this finding, we defined three subtypes of fenestral OS lesions that are suitable for clinical diagnosis guidance: "focal", "transitional", and "typical" fenestral OS. The most encouraging result is that the model achieved an area under the curve (AUC) of 99.5% (per-ear-sensitivity of 96.4%, per-ear-specificity of 98.9%) on the prospective unknown external test. Furthermore, we used this model to assist otologists and observed a consistent and significant improvement in diagnostic performance, especially for the newly defined focal and transitional fenestral OS, which led to the initial high misdiagnosis rate. CONCLUSIONS: Our findings of the fine-grained classification of fenestral OS could have implications for future diagnosis and prevention programs. In addition, our deep OS localization network is an effective approach providing assistance to otologists to deal with the significant challenge of the misdiagnosis of fenestral OS.

Quantification of sorafenib, lenvatinib, and apatinib in human plasma for therapeutic drug monitoring by UPLC-MS/MS.

Sorafenib, lenvatinib, and apatinib, as multi-targeted tyrosine kinase inhibitors with anti-proliferative and anti-angiogenic effects, are widely used for systemic therapy in advanced hepatocellular carcinoma patients. Nevertheless, insufficient efficacy or adverse effects often appear due to the significant inter-individual variability of plasma concentration for these drugs. In order to carry out therapeutic drug monitoring of these drugs and then ensure the effectiveness and safety of the medical treatment, the first method allowing to quantify sorafenib, lenvatinib, and apatinib simultaneously in human plasma was developed in this study. The analysis was performed by UPLC-MS/MS system and the chromatographic separation was achieved on a C18 column using a gradient elution of water-acetonitrile in 3.5 min. This method presented satisfactory results in terms of specificity, precision (coefficient of variation of intra-day and inter-day:1.4-6.6 %), accuracy (92.6-105.4 %), matrix effects (96.9-107.2 %), extraction recovery (90.5-99.4 %), as well as stability in human plasma and even whole blood under certain conditions. This sensitive, rapid and simple method was successfully applied to the analysis of sorafenib, lenvatinib and apatinib for therapeutic drug monitoring in hepatocellular carcinoma patients, and it was expected to be applied to further study about clarifying the concentration- efficacy and concentration-toxic relationship of sorafenib, lenvatinib, and apatinib in hepatocellular carcinoma patients.

Dual-energy CT in predicting Ki-67 expression in laryngeal squamous cell carcinoma.

PURPOSE: To investigate whether multiple dual-energy computed tomography (DECT) parameters can noninvasively predict the Ki-67 expression (associated with survival and prognosis) in laryngeal squamous cell carcinoma (LSCC). METHODS: Eighty-eight patients with histologically proven LSCC were retrospectively reviewed. Multiple DECT-derived parameters were measured and correlated with Ki-67 expression by Spearman correlation analysis. Comparisons of the DECT-derived parameters between tumors with low- and high-level expression of Ki-67 were made with the t-tests. RESULTS: The iodine concentration (IC), normalized IC (NIC), effective atomic number (Zeff), 40-80 keV, and slope (k) values were positively correlated with Ki-67 expression (all p < 0.05, rho=0.367-0.548). Among all DECT-derived parameters, NIC value had the highest r value in correlation with Ki-67 expression. The IC, NIC, Zeff, 40-80 keV, and slope (k) values were significantly higher in LSCC with high Ki-67 expression than in those with low Ki-67 expression (all p < 0.05). CONCLUSIONS: Multiple DECT-derived parameters (IC, NIC, Zeff, 40-80 keV, and slope (k)) can be used as predictors of survival and prognosis in LSCC, among which the NIC value is the strongest.

Dynamic monitoring of serum liver function indexes in patients with COVID-19.

BACKGROUND: Some patients with the novel 2019 coronavirus disease (COVID-19) display elevated liver enzymes. Some antiviral drugs that can be used against COVID-19 are associated with a risk of hepatotoxicity. AIM: To analyze the clinical significance of the dynamic monitoring of the liver function of patients with COVID-19. METHODS: This was a retrospective study of patients diagnosed with COVID-19 in January and February 2020 at the Department of Infection, Shantou Central Hospital. The exclusion criteria for all patients were: (1) History of chronic liver disease; (2) History of kidney disease; (3) History of coronary heart disease; (4) History of malignancy; or (5) History of diabetes. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase, and total bilirubin of patients with COVID-19 were measured on days 1, 3, 7 and 14 after admission, and compared to non-COVID-19 patents. RESULTS: Twelve patients with COVID-19 (seven men and five women) and twelve controls (eight men and four women) were included. There were one, two, and nine patients with severe, mild, and moderate COVID-19, respectively. There were no differences in age and sex between the two groups (both P > 0.05). No significant differences were found in albumin, ALT, AST, γ-glutamyltransferase, or total bilirubin between the controls and the patients with COVID-19 on day 1 of hospitalization (all P > 0.05). Serum albumin showed a decreasing trend from days 0 to 7 of hospitalization, reaching the lowest level on day 7. Total bilirubin was higher on day 3 than on day 7. ALT, AST, and γ-glutamyltransferase did not change significantly over time. The severe patient was observed to have ALT levels of 67 U/L and AST levels of 75 U/L on day 7, ALT of 71 U/L and AST of 35 U/L on day 14, and ALT of 210 U/L and AST of 123 U/L on day 21. CONCLUSION: Changes in serum liver function indicators are not obvious in the early stage of COVID-19, but clinically significant changes might be observed in severe COVID-19.

Altered spontaneous neuronal activity and functional connectivity pattern in primary angle-closure glaucoma: a resting-state fMRI study.

PURPOSE: To explore the alterations of spontaneous neuronal activity and functional connectivity pattern using fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) in patients with primary angle-closure glaucoma (PACG) and fALFF relationship with the glaucoma clinical indices. MATERIALS AND METHODS: Forty-two PACG patients and 21 normal controls were enrolled in this study. Resting-state functional magnetic resonance imaging was firstly analyzed by fALFF and brain regions with altered fALFF between groups were selected as seeds for the further FC analysis. The relationships between fALFF/FC values of abnormal regions and ophthalmological measures, including mean deviation of visual field (MDVF) and retinal nerve fiber layer (RNFL) thickness, were also analyzed. RESULTS: Compared with NC, PACG had significant lower fALFF values in the left cuneus, left middle temporal gyrus, right middle temporal gyrus, and right precentral gyrus, while higher fALFF values in the bilateral superior frontal gyrus (P < 0.05 after correction). Furthermore, PACG showed increased FC between left cuneus and bilateral superior frontal gyrus/bilateral posterior cingulate gyrus; between left middle temporal gyrus and bilateral superior frontal gyrus; and between right middle temporal gyrus and bilateral insular (P < 0.05 after correction). In addition, in the PACG group, the mean fALFF values of the left cuneus were positively correlated with MDVF (R = 0.419, P = 0.005) and RNFL thickness (R = 0.322, P = 0.038). Meanwhile, the mean fALFF values of bilateral superior frontal gyrus were negatively correlated with MDVF (R = - 0.454, P = 0.003) and RNFL thickness (R = - 0.556, P < 0.001). CONCLUSIONS: PACG exhibited abnormal spontaneous neural activity and connectivity in several brain regions mainly associated with visual and visual-related functions. In addition, the fALFF values of the left cuneus and bilateral superior frontal gyrus may be complementary biomarkers for assessing the disease severity.

Comparison of sample preparation methods, validation of an UPLC-MS/MS procedure for the quantification of cyclosporine A in whole blood sample.

Current main methods for therapeutic drug monitoring (TDM) of cyclosporine A (CsA) are immunoassays and liquid chromatography tandem mass spectrometry. The sample pretreatment of these methods is mainly based on extraction of drug which is bound to erythrocytes by divalent heavy metal ions (such as zinc and copper). Although these methods are effective for whole blood drug extraction and measurement, the pollution of heavy metals in sample pretreatment process will have potential negative impact on environment and human health. To overcome the pollution problem, in this study we have developed and validated an UPLC-MS/MS method for CsA determination in whole blood samples using physical pretreatment method. According to the characteristics of erythrocytes, a series of physical pretreatment methods, including sonication, freeze-thaw and osmotic burst, have been developed and evaluated. The results showed that the osmotic burst method was an effective way for drug extraction from erythrocytes. The lower limit of quantitation for CsA was 25 ng/mL, the within-run and between-run coefficient of variations were both less than 11.6 %. The agreement of the UPLC-MS/MS methods using these two sample pretreatment was evaluated by Bland-Altman plot and the two-tailed Student's T-test. Comparison studies show that the effect of erythrocyte fragmentation by osmotic burst is similar to that of zinc sulfate method. The CsA measurement of 103 whole blood samples obtained by these two UPLC-MS/MS assays were no significant difference. These results demonstrate that the sample pretreatment by osmotic burst method is an eco-friendly and precise method for detecting the whole blood CsA concentration and therapeutic drug monitoring of CsA.