Solid pseudopapillary neoplasm: Report of a case of primary ovarian origin and review of the literature.

Background: Solid pseudopapillary neoplasms (SPNs) are uncommon tumors of low malignancy with a generally favorable prognosis, mostly originating from the pancreas. To date, 12 cases of SPNs with a primary ovarian origin (SPN-Os) have been reported globally, and their detailed characteristics have not been fully elucidated. Case description: We reported the 13th SPN-O case, which occurred in a 52-year-old woman with an 18.5 cm left ovarian mass. Four imaging methods, including ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography, were utilized before surgery. An elevated level of serum cancer antigen 125 was detected and a total hysterectomy plus bilateral salpingo-oophorectomy was performed. Microscopic examination revealed a typical solid pseudopapillary structure. The tumor cells were stained focally for pan-cytokeratin, synaptophysin, CD99 and CD10, while ß-catenin, vimentin and CD56 were diffusely expressed. The Ki-67 proliferation index was 3%, and immunohistochemical (IHC) staining for chromogranin-A, inhibin-a, and E-cadherin was negative. No evidence of recurrence or metastasis was observed by clinical and imaging data during a 5-month postoperative follow-up. Conclusion: This is a report of an unusual case of a primary ovarian SPN with an up-to-date review of SPN-Os. A minimum combination of imaging methods and IHC stains was proposed for SPN-Os, which may prove beneficial in clinical practice.

White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study.

PURPOSE: To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). METHODS: Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. RESULTS: MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. CONCLUSION: MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.

Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: A neurite orientation dispersion and density imaging study.

AIMS: To investigate microstructural impairments of corticospinal tracts (CSTs) with different origins in amyotrophic lateral sclerosis (ALS) using neurite orientation dispersion and density imaging (NODDI). METHODS: Diffusion-weighted imaging data acquired from 39 patients with ALS and 50 controls were used to estimate NODDI and diffusion tensor imaging (DTI) models. Fine maps of CST subfibers originating from the primary motor area (M1), premotor cortex, primary sensory area, and supplementary motor area (SMA) were segmented. NODDI metrics (neurite density index [NDI] and orientation dispersion index [ODI]) and DTI metrics (fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) were computed. RESULTS: The patients with ALS showed microstructural impairments (reflected by NDI, ODI, and FA reductions and MD, AD, and RD increases) in CST subfibers, especially in M1 fibers, which correlated with disease severity. Compared with other diffusion metrics, NDI yielded a higher effect size and detected the greatest extent of CST subfibers damage. Logistic regression analyses based on NDI in M1 subfiber yielded the best diagnostic performance compared with other subfibers and the whole CST. CONCLUSIONS: Microstructural impairment of CST subfibers (especially those originating from M1) is the key feature of ALS. The combination of NODDI and CST subfibers analysis may improve diagnosing performance for ALS.

Altered isotropic volume fraction in gray matter after sleep deprivation and its association with visuospatial memory: A neurite orientation dispersion and density imaging study.

Background and aims: Diffusion magnetic resonance imaging (dMRI) studies have revealed microstructural abnormalities in white matter resulting from sleep deprivation (SD). This study aimed to adopt neurite orientation dispersion and density imaging (NODDI) to investigate the effect of SD on gray matter (GM) microstructural properties and its association to visuospatial memory (VSM). Methods: Twenty-four healthy women underwent two sessions of dMRI scanning and visuospatial ability assessment by Complex Figure Test (CFT), once during rested wakefulness (RW) and once after 24 h of SD. We calculated NODDI metrics, including intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISO). Differences in NODDI-related metrics between RW and SD were determined using a voxel-wise paired t-test. We identified an association between NODDI metrics and CFT results using Spearman's correlation coefficient. Results: Sleep deprivation worsened subjects' performance in the delayed-CFT trial. We observed no significant difference in ICVF and ODI between RW and SD. After SD, subjects showed decreases in ISO, primarily in the prefrontal cortex and temporal lobe, while exhibiting ISO increases in the anterior and posterior cerebellar lobe and cerebellar vermis. Furthermore, ISO change in the left superior, middle and inferior frontal gyrus was significantly correlated with completion time change in delayed-CFT trial performance. Conclusion: Our results suggested that SD hardly affected the density and spatial organization of neurites in GM, but the extra-neurite water molecule diffusion process was affected (perhaps resulting from neuroinflammation), which contributed to VSM dysfunction.

A comparison of special intrauterine balloons and intrauterine contraceptive devices in the treatment of intrauterine adhesions.

PURPOSE: This study aimed to compare the efficacy of a special kind of intrauterine balloon (IUB) and that of an intrauterine contraception device (IUD) for patients with intrauterine adhesions (IUAs) after transcervical resection of adhesion (TCRA). METHODS: In this retrospective cohort study, after TCRA, 31 patients received a special IUB, and 38 patients received an IUD. The Fisher exact test, logistic regression method, Kaplan-Meier method and Cox proportional hazards regression model were used for statistical analysis. A two-sided value of P < 0.05 was considered statistically significant. RESULTS: The readhesion rate significantly differed between the IUB group and IUD group, at 15.39% and 54.06%, respectively (P = 0.002). For recurrent moderate IUA, patients in the IUB group had lower scores than patients in the IUD group (P = 0.035). There was a significant difference in the intrauterine pregnancy rate of IUA patients in the IUB group and IUD group after treatment, with rates of 55.56% and 14.29%, respectively (P = 0.015). CONCLUSION: Patients in the special IUB group had better outcomes than those in the IUD group, which has a certain guiding significance for clinical work.

Five New Phenylpropanoyl Phloroglucinol Derivatives from Leptospermum scoparium.

Leptosperols C-G (1-5), five new phenylpropanoyl phloroglucinol derivatives were isolated from the leaves of Leptospermum scoparium. Compounds 1-3 are phenylpropanoyl phloroglucinol-sesquiterpene adducts with new carbon skeletons. Their structures with absolute configurations were elucidated by detailed spectroscopic analyses, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculation. Compounds 2 and 3 exhibited moderate anti-inflammatory activity in zebrafish acute inflammatory models.

Altered dynamic brain activity and its association with memory decline after night shift-related sleep deprivation in nurses.

AIMS AND OBJECTIVES: To investigate, for the first time, aberrant time-varying local brain activity in nurses following night shift-related sleep deprivation (SD) and its association with memory decline. BACKGROUND: Prior studies have elucidated alterations in static local brain activity resulting from SD in the occupations outside medical profession. DESIGN: A longitudinal study followed the STROBE recommendations. METHODS: Twenty female nurses underwent resting-state functional magnetic resonance imaging and memory function assessment (by Complex Figure Test (CFT) and the California Verbal Learning Test, Second Edition (CVLT-II)) twice, once in a rested wakefulness (RW) state and another after SD. By combining the sliding-window approach and amplitude of low-frequency fluctuation (ALFF) analysis, the dynamic ALFF (dALFF) variability was calculated to reflect the characteristics of dynamic local brain activity. RESULTS: Poor performance on the CFT and CVLT-II was observed in nurses with night shift-related SD. Reduced dALFF variability was found in a set of cognition-related brain regions (including the medial/middle/superior frontal gyrus, anterior/posterior cingulate gyrus, precuneus, angular gyrus, orbitofrontal and subgenual areas, and posterior cerebellum lobe), while increased dALFF variability was observed in the somatosensory-related, visual and auditory regions. SD-related dALFF variability alterations correlated with changes in subjects' performance on the CFT and CVLT-II. CONCLUSIONS: Night shift-related SD disturbed dynamic brain activity in high cognitive regions and induced compensatory reactions in primary perceptual cortex. Identifying dALFF variability abnormalities may broaden our understanding of neural substrates underlying SD-related cognitive alterations, especially memory dysfunction. RELEVANCE TO CLINICAL PRACTICE: Night shift-related SD is as an important occupational hazard affecting brain function in nurses. The effective countermeasure addressing the adverse outcomes of SD should be advocated for nurses. PATIENT OR PUBLIC CONTRIBUTION: Patients or public were not involved in the design and implementation of the study or the analysis and interpretation of the data.

Altered stability of brain functional architecture after sleep deprivation: A resting-state functional magnetic resonance imaging study.

Background and aims: Resting-state functional magnetic resonance imaging (fMRI) studies using static and dynamic functional connectivity (FC) approaches have revealed brain dysfunction resulting from sleep deprivation (SD). The effects of SD on the stability of brain functional architecture remain unclear. This study investigated the functional stability (FS) changes induced by SD and its association with neurocognitive alterations. Materials and methods: In this study, we recruited 24 healthy women. All participants underwent two sessions of resting-state fMRI scanning and neurocognitive assessment. The assessments included the Digit Symbol Test, Digit Span Test, Trail-Making Test (TMT), and Complex Figure Test (CFT). Participants completed one session under rested wakefulness (RW) and one session after SD for 24 h. To estimate dynamic FC, we used the sliding window approach; and then, to characterize the FS of each voxel, we measured dynamic FC concordance over time. We used a paired t-test to identify differences in FS between RW and SD. To examine the relationship between these changes in FS and alterations in neurocognitive performance, we conducted Spearman's correlation analyses. Results: SD affected the performance of the Digit Symbol Test, Digit Span Test, and CFT. Compared with RW, subjects with SD exhibited decreased FS in the bilateral anterior and posterior cingulate gyrus and medial frontal gyrus, right superior frontal gyrus, and cerebellum posterior lobe, while they exhibited increased FS in the bilateral precentral/postcentral gyrus and supplementary motor area, right parahippocampal gyrus and fusiform gyrus, left inferior occipital gyrus, and bilateral cerebellum anterior lobe. After SD, FS changes in the right parahippocampal gyrus and fusiform gyrus were correlated with altered performance in the Digit Symbol Test and CFT. Conclusion: Our findings showed that the stability of the brain's functional architecture could be altered by SD. This stability alteration may correspond to multiple neurocognitive domain changes.

Palladium-platinum bimetallic nanomaterials and their application in Staphylococcus aureus detection on paper-based devices.

In this study, we demonstrate how palladium@platinum nanoparticles (Pd@Pt NPs) can be used as a nanozyme for the detection of Staphylococcus aureus (S. aureus) on a paper-based analytical device. Pt was doped with Pd to form bimetallic NPs that serve as a peroxidase mimetic, which can enhance the reaction area with a substrate (3, 3', 5, 5'-tetramethylbenzidine, TMB). After material characterization, we show the peroxidase-like activity of the Pd@Pt NPs featured a 13-times higher binding affinity value (Km) for TMB compared to horseradish peroxidase, which is currently widely used in immunoassays. By incorporating the Pd@Pt NPs in a paper-based immunoassay, we can detect protein A, the biomarker of S. aureus, within 30 min with a detection limit of 9.56 ng/mL. We have also successfully validated this nanozyme-immobilized paper-based analytical device (nPAD) for the detection of human immunoglobulin G to demonstrate the capability of the Pd@Pt NPs for different target analytes. This highly sensitive, rapid, and portable nPAD design has the potential for personalized medicine and point-of-care testing, which could expand on-site prognoses in resource-limited settings.

Promoting effect of Fe3+ on gentamicin resistance in Escherichia coli.

Kinds of antibiotics are used to prevent and control bacteria infections, unfortunately, the overuse and misuse of antibiotic have promoted the emergence and spread of antibiotic-resistant bacteria. Therefore, understanding the mechanism of antibiotic resistance is very important. This study explores the combined effection of metal ions and antibiotic to the drug resistance of Escherichia coli. Our results found that the minimum inhibitory concentration (MIC) increased as the ammonium ferric citrate concentration increased, especially for gentamicin antibiotic. When the Fe3+ concentration reached 300 µM, the survival of E. coli was stably restored with the increased gentamicin concentration. Exogenous Fe3+ could decrease intracellular gentamicin concentration. On the other hand, Fe3+ treatment together with gentamicin could reduce reactive oxygen species (ROS) production, characterized by decreased levels of NADH and ATP. Furthermore, ROS-scavenging enzymes of superoxide dismutase (SOD) and catalase (CAT) were up-regulated and H2O2 plus gentamicin-mediated killing was restored by Fe3+. These results may have significant implications in understanding bacterial antibiotic-resistant mechanisms based on the external Fe3+ concentration.

Dynamic Alterations in Functional Connectivity Density in Amyotrophic Lateral Sclerosis: A Resting-State Functional Magnetic Resonance Imaging Study.

Background and Aims: Current knowledge on the temporal dynamics of the brain functional organization in amyotrophic lateral sclerosis (ALS) is limited. This is the first study on alterations in the patterns of dynamic functional connection density (dFCD) involving ALS. Methods: We obtained resting-state functional magnetic resonance imaging (fMRI) data from 50 individuals diagnosed with ALS and 55 healthy controls (HCs). We calculated the functional connectivity (FC) between a given voxel and all other voxels within the entire brain and yield the functional connection density (FCD) value per voxel. dFCD was assessed by sliding window correlation method. In addition, the standard deviation (SD) of dFCD across the windows was computed voxel-wisely to measure dFCD variability. The difference in dFCD variability between the two groups was compared using a two-sample t-test following a voxel-wise manner. The receiver operating characteristic (ROC) curve was used to assess the between-group recognition performance of the dFCD variability index. Results: The dFCD variability was significantly reduced in the bilateral precentral and postcentral gyrus compared with the HC group, whereas a marked increase was observed in the left middle frontal gyrus of ALS patients. dFCD variability exhibited moderate potential (areas under ROC curve = 0.753-0.837, all P < 0.001) in distinguishing two groups. Conclusion: ALS patients exhibit aberrant dynamic property in brain functional architecture. The dFCD evaluation improves our understanding of the pathological mechanisms underlying ALS and may assist in its diagnosis.

Characterizing Sensorimotor-Related Area Abnormalities in Amyotrophic Lateral Sclerosis: An Intravoxel Incoherent Motion Magnetic Resonance Imaging Study.

RATIONALE AND OBJECTIVES: To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. MATERIALS AND METHODS: IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. RESULTS: ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). CONCLUSION: These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

Correction notice to "Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model".

[This corrects the article DOI: 10.1177/1758835920922034.].

Abnormal Stability of Dynamic Functional Architecture in Amyotrophic Lateral Sclerosis: A Preliminary Resting-State fMRI Study.

Purpose: Static and dynamic analyses for identifying functional connectivity (FC) have demonstrated brain dysfunctions in amyotrophic lateral sclerosis (ALS). However, few studies on the stability of dynamic FC have been conducted among ALS patients. This study explored the change of functional stability in ALS and how it correlates with disease severity. Methods: We gathered resting-state functional magnetic resonance data from 20 patients with ALS and 22 healthy controls (HCs). The disease severity was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). We used a sliding window correlation approach to identify dynamic FC and measured the concordance of dynamic FC over time to obtain the functional stability of each voxel. We assessed the between-group difference in functional stability by voxel-wise two-sample t-test. The correlation between the functional stability index and ALSFRS-R in ALS patients was evaluated using Spearman's correlation analysis. Results: Compared with the HC group, the ALS group had significantly increased functional stability in the left pre-central and post-central gyrus and right temporal pole while decreased functional stability in the right middle and inferior frontal gyrus. The results revealed a significant correlation between ALSFRS-R and the mean functional stability in the right temporal pole (r = -0.452 and P = 0.046) in the ALS patients. Conclusions: ALS patients have abnormal stability of brain functional architecture, which is associated with the severity of the disease.

White matter microstructural impairments in amyotrophic lateral sclerosis: A mean apparent propagator MRI study.

BACKGROUND: White matter (WM) impairment is a hallmark of amyotrophic lateral sclerosis (ALS). This study evaluated the capacity of mean apparent propagator magnetic resonance imaging (MAP-MRI) for detecting ALS-related WM alterations. METHODS: Diffusion images were obtained from 52 ALS patients and 51 controls. MAP-derived indices [return-to-origin/-axis/-plane probability (RTOP/RTAP/RTPP) and non-Gaussianity (NG)/perpendicular/parallel NG (NG⊥/NG||)] were computed. Measures from diffusion tensor/kurtosis imaging (DTI/DKI) and neurite orientation dispersion and density imaging (NODDI) were also obtained. Voxel-wise analysis (VBA) was performed to determine differences in these parameters. Relationship between MAP parameters and disease severity (assessed by the revised ALS Functional Rating Scale (ALSFRS-R)) was evaluated by Pearson's correlation analysis in a voxel-wise way. ALS patients were further divided into two subgroups: 29 with limb-only involvement and 23 with both bulbar and limb involvement. Subgroup analysis was then conducted to investigate diffusion parameter differences related to bulbar impairment. RESULTS: The VBA (with threshold of P < 0.05 after family-wise error correction (FWE)) showed that ALS patients had significantly decreased RTOP/RTAP/RTPP and NG/ NG⊥/NG|| in a set of WM areas, including the bilateral precentral gyrus, corona radiata, posterior limb of internal capsule, midbrain, middle corpus callosum, anterior corpus callosum, parahippocampal gyrus, and medulla. MAP-MRI had the capacity to capture WM damage in ALS, which was higher than DTI and similar to DKI/NODDI. RTOP/RTAP/NG/NG⊥/NG|| parameters, especially in the bilateral posterior limb of internal capsule and middle corpus callosum, were significantly correlated with ALSFRS-R (with threshold of FWE-corrected P < 0.05). The VBA (with FWE-corrected P < 0.05) revealed the significant RTAP reduction in subgroup with both bulbar and limb involvement, compared with those with limb-only involvement. CONCLUSIONS: Microstructural impairments in corticospinal tract and corpus callosum represent the consistent characteristic of ALS. MAP-MRI could provide alternative measures depicting ALS-related WM alterations, complementary to the common diffusion imaging methods.

Conducting polymer-based sensors for food and drug analysis.

Conducting polymers (CPs) are a category of polymeric materials with conjugated main chains. The characteristic electrical and optical properties of CPs can be fine-tuned through controlling the doping states of CPs. Because of their long-term stability in water, CPs have been demonstrated as electroactive biointerfaces and electrode materials especially in aqueous environments. Serving as multifunctional interfaces and organic electrodes for the integration bioelectronics and devices, CPs have been studied and applied in various biological applications. This paper provides a review of conducting polymer-based electrochemical sensors, particularly those used in biological fields. General conducting polymers and derivatives and their main electrochemical sensing platforms with different design of devices are introduced. Cyclic voltammetry, differential pulse voltammetry, chronoamperometry, electrochemical impedance spectroscopy, and quartz crystal microbalance methods and their features are then explored as detection methods for the analysis of drugs and food. To enhance the sensitivity and lower the detection limit of sensing platforms, various CP-based nanocomposites have been designed and developed. Although the electrodes made of CP-based nanocomposites usually outperform those made of pristine CPs, more systematic studies are required to provide insights into the design of nanocomposite-based electrodes. More applications of CP-based sensors for advanced food and drug analyses are expected.

Enhanced Functionality of Dual-Gate Organic Transistors Based on Semiconducting/Insulating Polyblend-Induced Asymmetric Charge Modulation Layers.

Dual-gate organic thin-film transistors (DG-OTFTs) with enhanced functionality, including large current enhancement behavior, highly efficient threshold voltage controllability, and self-contained dual-mode logic gate features, are reported. These DG-OTFTs are based on a semiconducting/insulating polyblend-based active layer with asymmetric top and bottom charge modulation layers (atb-CMLs). The atb-CMLs are automatically generated through the preparation of multilayer stacks of phase-separated semiconducting poly(3-hexylthiophene) (P3HT):insulating poly(methylmethacrylate) (PMMA) polyblend layer, poly(vinylidene fluoride) (PVDF) layer, and cross-linked-poly(4-vinylphenol) (cPVP) layer. They consist of a thin PMMA bottom layer and an uneven-shaped PMMA:PVDF miscible mixture-based top layer. The presence of the polarizable insulating PMMA, PVDF, and PMMA:PVDF mixture regions causes the bottom and top CMLs to experience electrical polarization, which induces the dipole field to achieve efficient charge modulation functions in DG-OTFTs. Owing to the presence of atb-CMLs, the DG-OTFTs exhibit unprecedented electrical characteristics, such as the easy depletion of the bottom channel by the top gate potential. However, the top channel can work properly only when given a bottom gate potential (either positive or negative). Given these unusual electrical features, the design of the fundamental dual-mode logic gates (e.g., AND and OR gates) can be achieved with just one DG transistor. This finding opens an interesting direction for the preparation of DG-OTFTs with diverse operating modes and increasing functionality, thereby widening the application potential of such transistors.

A Multifunctional Microfluidic Device for Blood Typing and Primary Screening of Blood Diseases.

In this work, we demonstrate a multifunctional, portable, and disposable microfluidic device for blood typing and primary screening of blood diseases. Preloaded antibodies (anti-A, anti-B, and anti-D) interact with injected whole blood cells to cause an agglutination reaction that blocks a microslit in the microfluidic channel to accumulate red blood cells and form a visible red line that can be easily read to determine the blood type. Moreover, the different blood density and agglutination properties of normal and subtype blood groups, as well as different blood diseases, including anemia and polycythemia vera, generate different lengths of blood agglutination within the channels, which allows us to successfully screen these various conditions in as little as 2 min. The required blood volume for each test is just 1 µL, which can be obtained by minimally invasive finger pricking. This novel method of observing agglutinated red blood cells to distinguish blood types and diseases is both feasible and affordable, suggesting its promise for use in areas with limited resources.

Next-Generation Sequencing-Based Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma Predicts Hepatocellular Carcinoma Recurrence.

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner.

Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy. METHODS: In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse. RESULTS: Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response. CONCLUSION: Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.