Disruption of the PGE2 synthesis / response pathway restrains atherogenesis in programmed cell death-1 (Pd-1) deficient hyperlipidemic mice.

Immune checkpoint inhibitors (ICIs) that target programmed cell death 1 (PD-1) have revolutionized cancer treatment by enabling the restoration of suppressed T-cell cytotoxic responses. However, resistance to single-agent ICIs limits their clinical utility. Combinatorial strategies enhance their antitumor effects, but may also enhance the risk of immune related adverse effects of ICIs. Prostaglandin (PG) E2, formed by the sequential action of the cyclooxygenase (COX) and microsomal PGE synthase (mPGES-1) enzymes, acting via its E prostanoid (EP) receptors, EPr2 and EPr4, promotes lymphocyte exhaustion, revealing an additional target for ICIs. Thus, COX inhibitors and EPr4 antagonists are currently being combined with ICIs potentially to enhance antitumor efficacy in clinical trials. However, given the cardiovascular (CV) toxicity of COX inhibitors, such combinations may increase the risk particularly of CV AEs. Here, we compared the impact of distinct approaches to disruption of the PGE2 synthesis /response pathway - global or myeloid cell specific depletion of mPges-1 or global depletion of Epr4 - on the accelerated atherogenesis in Pd-1 deficient hyperlipidemic (Ldlr-/-) mice. All strategies restrained the atherogenesis. While depletion of mPGES-1 suppresses PGE2 biosynthesis, reflected by its major urinary metabolite, PGE2 biosynthesis was increased in mice lacking EPr4, consistent with enhanced expression of aortic Cox-1 and mPges-1. Deletions of mPges-1 and Epr4 differed in their effects on immune cell populations in atherosclerotic plaques; the former reduced neutrophil infiltration, while the latter restrained macrophages and increased the infiltration of T-cells. Consistent with these findings, chemotaxis by bone-marrow derived macrophages from Epr4-/- mice was impaired. Epr4 depletion also resulted in extramedullary lymphoid hematopoiesis and inhibition of lipoprotein lipase activity (LPL) with coincident spelenomegaly, leukocytosis and dyslipidemia. Targeting either mPGES-1 or EPr4 may restrain lymphocyte exhaustion while mitigating CV irAEs consequent to PD-1 blockade.

ALDH2 is a novel biomarker and exerts an inhibitory effect on melanoma.

Melanoma is a malignant skin tumor. This study aimed to explore and assess the effect of novel biomarkers on the progression of melanoma. Differently expressed genes (DEGs) were screened from GSE3189 and GSE46517 datasets of Gene Expression Omnibus database using GEO2R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted based on the identified DEGs. Hub genes were identified and assessed using protein-protein interaction networks, principal component analysis, and receiver operating characteristic curves. Quantitative real-time polymerase chain reaction was employed to measure the mRNA expression levels. TIMER revealed the association between aldehyde dehydrogenase 2 (ALDH2) and tumor immune microenvironment. The viability, proliferation, migration, and invasion were detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays. Total 241 common DEGs were screened out from GSE3189 and GSE46517 datasets. We determined 6 hub genes with high prediction values for melanoma, which could distinguish tumor samples from normal samples. ALDH2, ADH1B, ALDH3A2, DPT, EPHX2, and GATM were down-regulated in A375 and SK-MEL-2 cells, compared with the human normal melanin cell line (PIG1 cells). ALDH2 was selected as the candidate gene in this research, presenting a high diagnostic and predictive value for melanoma. ALDH2 had a positive correlation with the infiltrating levels of immune cells in melanoma microenvironment. Overexpression of ALDH2 inhibited cell viability, proliferation, migration, and invasion of A375/SK-MEL-2 cells. ALDH2 is a new gene biomarker of melanoma, which exerts an inhibitory effect on melanoma.

Identifying IDH-mutant and 1p/19q noncodeleted astrocytomas from nonenhancing gliomas: Manual recognition followed by artificial intelligence recognition.

Background: The T2-FLAIR mismatch sign (T2FM) has nearly 100% specificity for predicting IDH-mutant and 1p/19q noncodeleted astrocytomas (astrocytomas). However, only 18.2%-56.0% of astrocytomas demonstrate a positive T2FM. Methods must be considered for distinguishing astrocytomas from negative T2FM gliomas. In this study, positive T2FM gliomas were manually distinguished from nonenhancing gliomas, and then a support vector machine (SVM) classification model was used to distinguish astrocytomas from negative T2FM gliomas. Methods: Nonenhancing gliomas (regardless of pathological type or grade) diagnosed between January 2022 and October 2022 (N = 300) and November 2022 and March 2023 (N = 196) will comprise the training and validation sets, respectively. Our method for distinguishing astrocytomas from nonenhancing gliomas was examined and validated using the training set and validation set. Results: The specificity of T2FM for predicting astrocytomas was 100% in both the training and validation sets, while the sensitivity was 42.75% and 67.22%, respectively. Using a classification model of SVM based on radiomics features, among negative T2FM gliomas, the accuracy was above 85% when the prediction score was greater than 0.70 in identifying astrocytomas and above 95% when the prediction score was less than 0.30 in identifying nonastrocytomas. Conclusions: Manual screening of positive T2FM gliomas, followed by the SVM classification model to differentiate astrocytomas from negative T2FM gliomas, may be a more effective method for identifying astrocytomas in nonenhancing gliomas.

Distinguishing Tumor Cell Infiltration and Vasogenic Edema in the Peritumoral Region of Glioblastoma at the Voxel Level via Conventional MRI Sequences.

RATIONALE AND OBJECTIVES: The peritumoral region of glioblastoma (GBM) is composed of infiltrating tumor cells and vasogenic edema, which are difficult to distinguish manually on MRI. To distinguish tumor cell infiltration and vasogenic edema in GBM peritumoral regions, it is crucial to develop a method that is precise, effective, and widely applicable. MATERIALS AND METHODS: We retrieved the image characteristics of 379,730 voxels (marker of tumor infiltration) from 28 non-enhanced gliomas and 365,262 voxels (marker of edema) from the peritumoral edema region of 14 meningiomas on conventional MRI sequences (T1-weighted image, the contrast-enhancing T1-weighted image, the T2-weighted image, the T2-fluid attenuated inversion recovery image, and the apparent diffusion coefficient map). Using the SVM classifier, a model for predicting tumor cell infiltration and vasogenic edema at the voxel level was developed. The accuracy of the model's predictions was then evaluated using 15 GBM patients who underwent stereotactic biopsies. RESULTS: The area under the curve (AUC), accuracy, sensitivity, and specificity of the prediction model were 0.93, 0.84, 0.83, and 0.85 in the training set, and 0.90, 0.82, 0.83, and 0.83 in the test set (704,992 voxels), respectively. The pathology verification of 28 biopsy points with an accuracy of 0.79. CONCLUSION: At the voxel level, it seems possible to forecast tumor cell infiltration and vasogenic edema in the peritumoral region of GBM based on conventional MRI sequences.

Elevated tissue transglutaminase levels in aqueous humor of congenital cataractous eyes with long axial length.

Objective: To investigate the distribution of axial length (AL) and posterior staphyloma (PS) in congenital cataract (CC) patients. The correlation between AL and the concentration of tissue transglutaminase (TGM2) in the aqueous humor (AH) of cataractous eyes was also evaluated. Methods: Cross-sectional data were collected from 499 children with CC who underwent phacoemulsification, anterior vitrectomy, and IOL implantation. AL measured by IOLMaster or A-scan ultrasonography and the presence of PS examined by B-scan ultrasonography were recorded. TGM2 levels in AH of 15 CC patients with normal axial length (NAL) and 15 CC patients with PS or long axial length (LAL) were measured by enzyme-linked immunosorbent assay. Results: The presence of PS in congenital cataractous eyes was 11.02%, and the presence of PS + LAL in congenital cataractous eyes was 29.06%. The AH levels of TGM2 in the cataractous group with NAL were lower than those in the cataractous group with PS or LAL (P < 0.001). The concentration of TGM2 in AH were positively correlated with AL of the patients' eyes (P = 0.001). Additionally, we found that TGM2 expressed in the cytoplasm of lens epithelial cells of cataractous eyes, and the expression level increased with the AL value. Conclusions: This study begins to lay the groundwork for investigating the characteristics of PS and LAL in patients with CC. Furthermore, AL was positively correlated with AH levels of TGM2.

Identification of Endometrial Cancer-Specific microRNA Biomarkers in Endometrial Fluid.

Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.

Epilepsy-related white matter network changes in patients with frontal lobe glioma.

PURPOSE: Epilepsy is a common symptom in patients with frontal lobe glioma. Tumor-related epilepsy was recently considered a type of network disease. Glioma can severely influence the integrity of the white matter network. The association between white matter network changes and presurgical epilepsy remains unclear in glioma patients. This study aims to identify alterations to the subcortical brain networks caused by glioma and glioma-related epilepsy. METHODS: Sixty-one patients with frontal lobe gliomas were enrolled and stratified into the epileptic and non-epileptic groups. Additionally, 14 healthy participants were enrolled after matching for age, sex, and education level. All participants underwent diffusion tensor imaging. Graph theoretical analysis was applied to reveal topological changes in their white matter networks. Regions affected by tumors were excluded from the analysis. RESULTS: Global efficiency was significantly decreased (p = 0.008), while the shortest path length increased (p = 0.02) in the left and right non-epileptic groups compared to the controls. A total of five edges exhibited decreased fiber count in the non-epileptic group (p < 0.05, false discovery rate-corrected). The topological properties and connectional edges showed no significant differences when comparing the epileptic groups and the controls. Additionally, the degree centrality of several nodes connected to the alternated edges was also diminished. CONCLUSIONS: Compared to the controls, the epilepsy groups showed raletively intact WM networks, while the non-epileptsy groups had damaged network with lower efficiency and longer path length. These findings indicated that the occurrence of glioma related epilepsy have association with white matter network intergrity.

Three amino acid substitutions contributing to thermostability of phosphoglucose isomerase in the Glanville fritillary butterfly.

Temperature is one of the most important environmental factors that affect organisms, especially ectotherms, due to its effects on protein stability. Understanding the general rules that govern thermostability changes in proteins to adapt high-temperature environments is crucial. Here, we report the amino acid substitutions of phosphoglucose isomerase (PGI) related to thermostability in the Glanville fritillary butterfly (Melitaea cinxia, Lepidoptera: Nymphalidae). The PGI encoded by the most common allele in M. cinxia in the Chinese population (G3-PGI), which is more thermal tolerant, is more stable under heat stress than that in the Finnish population (D1-PGI). There are 5 amino acid substitutions between G3-PGI and D1-PGI. Site-directed mutagenesis revealed that the combination of amino acid substitutions of H35Q, M49T, and I64V may increase PGI thermostability. These substitutions alter the 3D structure to increase the interaction between 2 monomers of PGI. Through molecular dynamics simulations, it was found that the amino acid at site 421 is more stable in G3-PGI, confining the motion of the α-helix 420-441 and stabilizing the interaction between 2 PGI monomers. The strategy for high-temperature adaptation through these 3 amino acid substitutions is also adopted by other butterfly species (Boloria eunomia, Aglais urticae, Colias erate, and Polycaena lua) concurrent with M. cinxia in the Tianshan Mountains of China, i.e., convergent evolution in butterflies.

Prognostic significance of tumor deposits in radically resected gastric cancer: a retrospective study of a cohort of 1915 Chinese individuals.

BACKGROUND: Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients. METHODS: We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted. RESULTS: The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance. CONCLUSIONS: The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.

Development and validation of a novel survival prediction model for newly diagnosed lower-grade gliomas.

OBJECTIVE: Diffuse gliomas are the most common primary gliomas with a poor prognosis. This study aimed to develop and validate prognostic models for predicting the survival probability in newly diagnosed lower-grade glioma (LGG) patients. METHODS: Detailed data were obtained for newly diagnosed LGG from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. Survival was assessed using Cox proportional hazards regression with adjustment for known prognostic factors. The model was established using the TCGA cohort, and independently validated using the CGGA cohort, to predict the 3-, 5-, and 10-year survival probabilities of patients. RESULTS: Data from 293 patients with newly diagnosed LGG from the TCGA cohort were used to establish a prognostic model, and from 232 patients with primary LGG in the CGGA cohort to validate the model. Age, tumor grade, molecular subtype, tumor resection, and preoperative neurological deficits were included in the prediction model. The Cox regression model had a satisfactory corrected concordance index of 0.8508, 0.8510, and 0.8516 in the internal bootstrap validation at 3, 5, and 10 years, respectively. The calibration plots demonstrated high consistency of the predicted and observed outcomes. The CGGA cohort was used for external validation and showed satisfactory discrimination of 0.7776, 0.7682, and 0.7051 at 3, 5, and 10 years, respectively. The calibration plots demonstrated an acceptable calibration capability in the external validation. CONCLUSIONS: This study established and validated a prognostic model to predict the survival probability of patients with newly diagnosed LGG. The model performed well in discrimination and calibration with ease of use, speed, accessibility, interpretability, and generalizability. An easily used nomogram based on the Cox model was established for clinical application. Moreover, a free, easy-to-use software interface based on the nomogram is provided online.

Management of central nervous system Rosai-Dorfman disease: A single center treatment experience.

Rosai-Dorfman disease (RDD) is an idiopathic histiocytic proliferation disease with various clinical manifestations. A retrospective study of patients with pathological diagnosed RDD primarily involved in the central nervous system was conducted from January 2011 to December 2020 at a tertiary center. The clinical profile, imaging, and treatment data were collected. There were 16 male and 5 female patients with RDD-CNS. The patients were aged from 6 to 68 years with a median of 37 years. Of these 21 patients, 15 presented with intracranial RDD and 6 with spinal RDD. The main symptoms of RDD-CNS included headache, epilepsy, and neurological deficits. 76.19% (16/21) of the patients showed dura-based, homogeneous enhancement lesion on magnetic resonance imaging (MRI). Twenty patients received surgery as first treatment, and one patient received biopsy after steroid therapy. Total lesion resection was achieved in 42.9% (9/21) of the patients, subtotal resection in 47.6% (10/21), and biopsy in 0.9% (2/21). The symptoms were alleviated or stayed stable. Some RDDs (80%, 4/5) in the skull base had some complications. The patients were followed up for 11-108 months with a median duration of 47 months. Lesion progression or recurrence was found in two patients. The various clinical manifestations, as well as the dura-based and homogenous enhancement imaging profiles of RDD-CNS patients pose a great diagnostic challenge for clinicians. Surgery is effective for RDD-CNS requiring treatment. Medical therapy and radiotherapy would be feasible as noninvasive treatments, varying degrees of efficacy. The overall prognosis of RDD-CNS is acceptable. Periodic long-term follow-up is necessary.

Two simple-to-use web-based nomograms to predict overall survival and cancer-specific survival in patients with extremity fibrosarcoma.

Background: Fibrosarcoma is a rare sarcoma of the soft tissue in adults, occurring most commonly in the extremities. This study aimed to construct two web-based nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in patients with extremity fibrosarcoma (EF) and validate it with multicenter data from the Asian/Chinese population. Method: Patients with EF in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were included in this study and were randomly divided into a training cohort and a verification cohort. The nomogram was developed based on the independent prognostic factors determined by univariate and multivariate Cox proportional hazard regression analyses. The predictive accuracy of the nomogram was validated with the Harrell's concordance index (C-index), receiver operating curve, and calibration curve. Decision curve analysis (DCA) was utilized to compare the clinical usefulness between the novel model and the existing staging system. Result: A total of 931 patients finally were obtained in our study. Multivariate Cox analysis determined five independent prognostic factors for OS and CSS, namely, age, M stage, tumor size, grade, and surgery. The nomogram and the corresponding web-based calculator were developed to predict OS (https://orthosurgery.shinyapps.io/osnomogram/) and CSS (https://orthosurgery.shinyapps.io/cssnomogram/) probability at 24, 36, and 48 months. The C-index of the nomogram was 0.784 in the training cohort and 0.825 in the verification cohort for OS and 0.798 in the training cohort and 0.813 in the verification cohort for CSS, respectively, indicating excellent predictive performance. The calibration curves showed excellent agreement between the prediction by the nomogram and actual outcomes. Additionally, the results of DCA showed that the newly proposed nomogram was significantly better than the conventional staging system with more clinical net benefits. The Kaplan-Meier survival curves showed that patients assigned into the low-risk group had a more satisfactory survival outcome than the high-risk group. Conclusion: In this study, we constructed two nomograms and web-based survival calculators including five independent prognostic factors for the survival prediction of patients with EF, which could help clinicians make personalized clinical decisions.

The impact of pre-operative axial length on myopic shift 3 years after congenital and developmental cataract surgery and intraocular lens implantation.

Purpose: To investigate the impact of the pre-operative axial length (AL) on myopic shift (MS) 3 years after primary intraocular lens (IOL) implantation in congenital/developmental cataract patients. Methods: A retrospective study of patients who underwent congenital/developmental cataract surgery and primary IOL implantation at age 2-3 years at EENT Hospital was conducted. All patients were followed up regularly for at least 3 years after surgery. Refractive outcomes, including spherical equivalent (SE) and MS, were collected at each follow-up. Results: Forty eyes from 40 patients were included. The mean age at surgery was 2.56 ± 0.57 years old, and the mean follow-up time was 3.05 ± 0.22 years. Patients were divided into two groups: Group 1 included 20 patients with longer pre-operative ALs (≥22 mm), and Group 2 included 20 patients with average pre-operative ALs (<22 mm). By the last follow-up, the MS was 2.13 (0.38, 2.63) D in Group 1 and 3.88 (2.85, 5.72) D in Group 2. The post-operative MS in Group 2 was statistically greater than that in Group 1 at 3 years after surgery (P < 0.001). Conclusion: In congenital/developmental cataract patients who underwent cataract extraction and primary IOL implantation at age 2-3 years, eyes with longer pre-operative ALs had a slower MS than those with average pre-operative ALs 3 years after surgery. This finding could have implications for the target refraction decision in congenital/developmental cataract surgery.

The utility of intraoperative ECoG in tumor-related epilepsy: Systematic review.

OBJECT: Epilepsy is one of the most common clinical manifestations of primary brain tumors. Intraoperative electrocorticography (ECoG) has been widely used in tumor resection. We aim to describe the indication and utility of ECoG during brain tumor surgery. METHODS: We performed a systematic review of the literature on the prognosis of tumor-related epilepsy surgery guided by intraoperative ECoG. The published studies were searched in PubMed, Embase, and Web of Science using the keyword 'seizure' or 'epilepsy' and 'electrocorticography' or 'ECoG'. Two reviewer authors screened studies and extracted data independently. RESULTS: Thirteen studies included 569 patients were finally selected, of which eight investigated medically intractable epilepsy. Three publications described temporal tumor-related epilepsy. All included studies were retrospective, and the age of all patients ranged from 1 to 71 years. The duration of epilepsy ranged from 1 month to 30 years. Patients with tumor-related epilepsy underwent surgical treatment with Engel I outcomes ranging from 56.5%-100%. CONCLUSION: Intraoperative ECoG is generally considered a useful technique in delineating epileptogenic areas and improving the prognosis of surgical treatment of tumor-related epilepsy. However, large-scale randomized control trials are still needed to verify these findings and formulate appropriate surgical strategies.

The Impact of Inflammatory Immune Reactions of the Vascular Niche on Organ Fibrosis.

Inflammation is a type of defense response against tissue damage, and can be mediated by lymphocytes and macrophages. Fibrosis is induced by tissue injury and inflammation, which leads to an increase in fibrous connective tissue in organs and a decrease in organ parenchyma cells, finally leading to organ dysfunction or even failure. The vascular niche is composed of endothelial cells, pericytes, macrophages, and hematopoietic stem cells. It forms a guiding microenvironment for the behavior of adjacent cells, and mainly exists in the microcirculation, including capillaries. When an organ is damaged, the vascular niche regulates inflammation and affects the repair of organ damage in a variety of ways, such as via its angiocrine function and transformation of myofibroblasts. In this paper, the main roles of vascular niche in the process of organ fibrosis and its mechanism of promoting the progress of fibrosis through inflammatory immunoregulation are summarized. It was proposed that the vascular niche should be regarded as a new therapeutic target for organ fibrosis, suggesting that antifibrotic effects could be achieved by regulating macrophages, inhibiting endothelial-mesenchymal transition, interfering with the angiocrine function of endothelial cells, and inhibiting the transformation of pericytes into myofibroblasts, thus providing new ideas for antifibrosis drug research.

A new GlcNAc-containing polysaccharide from Morchella importuna fruiting bodies: Structural characterization and immunomodulatory activities in vitro and in vivo.

This study investigated the purification and characterization of a new immunomodulatory GlcNAc-containing polysaccharide (MIPB70-1) from Morchella importuna with molecular weights of 20.6 kDa. Structural analysis indicated that MIPB70-1 was composed of GlcNAc:Gal:Glc:Man with molar ratios of 1.00:7.16:5.54:5.61, and its primary structure was characterized as a repeating unit consisting of →6)-α-D-Glcp-(1→, α-D-GlcpNAc-(1→, α-D-Galp-(1→, ß-D-Glcp-(1→, →6)-α-D-Manp-(1→, →4)-α-D-GlcpNAc-(1→, →4)-ß-D-Glcp-(1→, →3,6)-α-D-Manp-(1→, →2)-α-D-Galp-(1→, →2,3,6)-α-D-Manp-(1→. Immunological assays indicated that MIPB70-1 enhanced the phagocytic function and promoted the secretion of nitric oxide (NO) as well as cytokines through targeting Toll-like receptor 4 (TLR4) on macrophage membrane and activating the downstream signaling pathways in RAW 264.7 cells. MIPB70-1 regulated mouse immunity to counteract the immune damage caused by the chemotherapy drug cyclophosphamide (CTX) in vivo. Furthermore, MIPB70-1 enhanced the anti-tumor activity of doxorubicin (DOX) and inhibited the growth of tumors, by immunomodulation in the orthotopic murine model of 4T1 breast cancer. These results demonstrate the potential of this GlcNAc-containing polysaccharide as an immune enhancer.

Ginsenoside Rk1 protects human melanocytes from H2O2­induced oxidative injury via regulation of the PI3K/AKT/Nrf2/HO­1 pathway.

Vitiligo is a cutaneous depigmentation disorder caused by melanocyte injury or aberrant functioning. Oxidative stress (OS) is considered to be a major cause of the onset and progression of vitiligo. Ginsenoside Rk1 (RK1), a major compound isolated from ginseng, has antioxidant activity. However, whether RK1 can protect melanocytes against oxidative injury remains unknown. The aim of the present study was to investigate the potential protective effect of RK1 against OS in the human PIG1 melanocyte cell line induced with hydrogen peroxide (H2O2), and to explore its underlying mechanism. PIG1 cells were pretreated with RK1 (0, 0.1, 0.2 and 0.4 mM) for 2 h followed by exposure to 1.0 mM H2O2 for 24 h. Cell viability and apoptosis were determined with Cell Counting Kit­8 and flow cytometry assays, respectively. The activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH­Px) were analyzed using ELISA kits. Protein expression levels, including Bax, caspase­3, Bcl­2, phosphorylated­AKT, AKT, nuclear factor erythroid 2­related factor 2 (Nrf2), heme oxygenase­1 (HO­1), cytosolic Nrf2 and nuclear Nrf2, were analyzed using western blot analysis. In addition, the expression and localization of Nrf2 were detected by immunofluorescence. RK1 treatment significantly improved cell viability, reduced the apoptotic rate and increased the activity levels of SOD, CAT and GSH­Px in the PIG1 cell line exposed to H2O2. In addition, RK1 treatment notably induced Nrf2 nuclear translocation, increased the protein expression levels of Nrf2 and HO­1, and the ratio of phosphorylated­AKT to AKT in the PIG1 cells exposed to H2O2. Furthermore, LY294002 could reverse the protective effect of RK1 in melanocytes against oxidative injury. These data demonstrated that RK1 protected melanocytes from H2O2­induced OS by regulating Nrf2/HO­1 protein expression, which may provide evidence for the application of RK1 for the treatment of vitiligo.

The Application and Evaluation of Effective Quality Management by Objectives in Patient Care for Persistent Vacuum Sealing Drainage.

To investigate the application and evaluation of effective quality management by objectives in patient care for persistent vacuum sealing drainage (VSD), a total of 164 patients with fractures of the hands and feet combined with soft tissue damage admitted to the department of hand and foot surgery in a provincial tertiary hospital from January 2018 to January 2020 were selected as study subjects. The patients were randomly divided into observation and control groups based on the types of fractures, with 82 patients in each group, and both groups underwent VSD surgery for treatment. Both of the groups were cared for VSD using the original nursing model and were compared in terms of treatment compliance, wound recovery, the occurrence of complications, and patient satisfaction with nursing work. The treatment compliance of patients in the observation group was higher than that of the control group (P < 0.05). Moreover, the wound healing condition in the observation group and the postoperative wound recovery data were better. The hospitalization time and the number of replacement suckers were less (P < 0.05), which met the requirements of statistical research. This confirmed that the application of quality management by objectives in patient care can improve patient compliance with treatment, promote wound healing, reduce the occurrence of corresponding postoperative complications in patients, and improve patient satisfaction with health nursing, which can be promoted for use in the workplace.

Lipid mediator lipoxin A4 and its analog BML-111 exert antitumor effects in melanoma.

BACKGROUND: LipoxinA4 (LXA4) is an anti-inflammatory lipid mediator which was recently proposed to have antitumor potential. However, the therapeutic effect of LXA4 in melanoma is still unclear. This work aimed to investigate the function of LXA4 and its analog in melanoma invasion through in vivo and in vitro experiments. METHODS: The expression of the LXA4 receptor (ALXR) was detected in melanoma tissues and A375 human melanoma cells, using benign melanocytic nevi tissues and human melanocytes as negative controls, respectively. The invasive and apoptotic abilities of A375 cells in the presence or absence of LXA4 were examined by cell invasion assay and flow cytometric analysis. Finally, mice melanoma models were established, and the antitumor effects of BML-111 [5(S), 6(R)-7-trihydroxymethyl heptanoate], an agonist of ALXR, were examined in vivo. RESULTS: ALXR was abundantly expressed in human melanoma tissues. The ALXR messenger RNA (mRNA) and protein expression levels were higher in A375 melanoma cells than in the controls (P<0.05). LXA4 could significantly attenuate the invasion ability of A375 cells (P<0.05). This trend was further enhanced by BML-111, which tended to control the tumor development in A375 melanoma models. CONCLUSIONS: LXA4 and its analog BML-111 exert antitumor effects in vivo and in vitro, and may be potential therapeutic options for patients with invasive melanoma.

Structural characterization and immunomodulatory mechanisms of two novel glucans from Morchella importuna fruiting bodies.

Two novel glucans named MIPB50-W and MIPB50-S-1 were obtained from edible Morchella importuna with molecular weights (Mw) of 939.2 kDa and 444.5 kDa, respectively. MIPB50-W has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1→. Moreover, MIPB50-S-1 has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1 → 6)-α-d-Glcp-(1→. This is the first report about glucan found in Morchella mushrooms. Furthermore, MIPB50-W and MIPB50-S-1 strengthened the phagocytosis function and the promoted secretion of interleukins (IL)-6/tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which induced the activation of Toll-like receptor 2 (TLR2), TLR4 as well as mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Interestingly, MIPB50-S-1 performed the better immunomodulatory activity than that of MIPB50-W in almost all tests. Therefore, MIPB50-W and MIPB50-S-1 are potential immune-enhancing components of functional foods.