WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target.

BACKGROUND: Overexpression of Wilms' tumor-1 (WT1) transcription factor facilitates proliferation in acute myeloid leukemia (AML). However, whether WT1 is enriched in the leukemia-initiating cells (LICs) and leukemia stem cells (LSCs) and facilitates the self-renewal of LSCs remains poorly understood. METHODS: MLL-AF9-induced murine leukemia model was used to evaluate the effect of knockdown of wt1 on the self-renewal ability of LSC. RNA sequencing was performed on WT1-overexpressing cells to select WT1 targets. Apoptosis and colony formation assays were used to assess the anti-leukemic potential of a deubiquitinase inhibitor WP1130. Furthermore, NOD/SCID-IL2Rγ (NSG) AML xenotransplantation and MLL-AF9-induced murine leukemia models were used to evaluate the anti-leukemogenic potential of WP1130 in vivo. RESULTS: We found that wt1 is highly expressed in LICs and LSCs and facilitates the maintenance of leukemia in a murine MLL-AF9-induced model of AML. WT1 enhanced the self-renewal of LSC by increasing the expression of BCL2L2, a member of B cell lymphoma 2 (BCL2) family, by direct binding to its promoter region. Loss of WT1 impaired self-renewal ability in LSC and delayed the progression of leukemia. WP1130 was found to modify the WT1-BCL2L2 axis, and WP1130-induced anti-leukemic activity was mediated by ubiquitin proteasome-mediated destruction of WT1 protein. WP1130 induced apoptosis and decreased colony formation abilities of leukemia cells and prolonged the overall survival in the THP1-based xenograft NSG mouse model. WP1130 also decreased the frequency of LSC and prolonged the overall survival in MLL-AF9-induced murine leukemia model. Mechanistically, WP1130 induced the degradation of WT1 by positively affecting the ubiquitination of WT1 protein. CONCLUSIONS: Our results indicate that WT1 is required for the development of AML. WP1130 exhibits anti-leukemic activity by inhibiting the WT1-BCL2L2 axis, which may represent a new acute myeloid leukemia therapy target.

Prognosis models for severe and critical COVID-19 based on the Charlson and Elixhauser comorbidity indices.

Background: Corona Virus Disease 2019 (COVID-19) has become a global pandemic. This study established prognostic scoring models based on comorbidities and other clinical information for severe and critical patients with COVID-19. Material and Methods: We retrospectively collected data from 51 patients diagnosed as severe or critical COVID-19 who were admitted between January 29, 2020, and February 18, 2020. The Charlson (CCI), Elixhauser (ECI), and age- and smoking-adjusted Charlson (ASCCI) and Elixhauser (ASECI) comorbidity indices were used to evaluate the patient outcomes. Results: The mean hospital length of stay (LOS) of the COVID-19 patients was 22.82 ± 12.32 days; 19 patients (37.3%) were hospitalized for more than 24 days. Multivariate analysis identified older age (OR 1.064, P = 0.018, 95%CI 1.011-1.121) and smoking (OR 3.696, P = 0.080, 95%CI 0.856-15.955) as positive predictors of a long LOS. There were significant trends for increasing hospital LOS with increasing CCI, ASCCI, and ASECI scores (OR 57.500, P = 0.001, 95%CI 5.687-581.399; OR 71.500, P = 0.001, 95%CI 5.689-898.642; and OR 19.556, P = 0.001, 95%CI 3.315-115.372, respectively). The result was similar for the outcome of critical illness (OR 21.333, P = 0.001, 95%CI 3.565-127.672; OR 13.000, P = 0.009, 95%CI 1.921-87.990; OR 11.333, P = 0.008, 95%CI 1.859-69.080, respectively). Conclusions: This study established prognostic scoring models based on comorbidities and clinical information, which may help with the graded management of patients according to prognosis score and remind physicians to pay more attention to patients with high scores.

LncRNA MCM3AP-AS1 is downregulated in atherosclerosis and sponges miR-448 to suppress vascular smooth muscle cell proliferation.

Long noncoding RNA MCM3AP-AS1 plays critical roles in cancers, but its role in atherosclerosis is yet to be elucidated. The expression of MCM3AP-AS1 in atherosclerosis and control plasma samples were measured by RT-qPCR. IntaRNA was used to predict potential base pairings between MCM3AP-AS1 and miR-448, and the results were confirmed by a dual luciferase activity assay. Cell proliferation assay was performed to explore the role of overexpression of MCM3AP-AS1, miR-448, and myocyte enhancer factor 2 (MEF2)-C in the proliferation of human aortic smooth muscle cells (HAOSMCs). MCM3AP-AS1 was downregulated in atherosclerosis and directly interacted with miR-448, which is a critical player in the proliferation of HAOSMCs, indicating its involvement in atherosclerosis. However, MCM3AP-AS1 and miR-448 showed no role in regulating the expression of each other. In contrast, overexpression of MCM3AP-AS1 increased the expression levels of MEF2-C, which can be targeted by miR-448. Moreover, MCM3AP-AS1 was found to inhibit the effects of miR-448 overexpression on both HAOSMC proliferation and MEF2-C expression. MCM3AP-AS1 is downregulated in atherosclerosis and sponges miR-448 to suppress the proliferation of HAOSMCs.

CTRP3/AMPK pathway plays a key role in the anti-hypertrophic effects of cyanidin-3-O-glucoside by inhibiting the inflammatory response.

BACKGROUND: Cardiac hypertrophy can be a pathological process that impairs heart function. Anthocyanins are a well-characterized type of natural antioxidant, and recent studies have shown that this type of compound has potential cardioprotective effects against different disorders, such as cardiac hypertrophy. OBJECTIVES: We assessed the anti-hypertrophy potential of cyanidin-3-O-glucoside (C3G) and the mechanism associated with any observed effects. MATERIAL AND METHODS: Hypertrophy symptoms were induced using the transverse aortic constriction (TAC) operation in vivo and angiotensin II (Ang II) in vitro. The effect of C3G on the development of hypertrophic symptoms was then determined. Moreover, we examined the influence of CTRP3 inhibition on the anti-hypertrophy function of C3G. RESULTS: The TAC operation induced cardiac fibrosis and heart weight increase, which was associated with increased production of cytokines and suppressed activity of the CTRP3/AMPK pathway. The impairments of heart structure and function were attenuated by C3G. Angiotensin II induced size increases of neonatal rat cardiomyocytes (NRCMs) in vitro, and this effect was inhibited by C3G. Furthermore, the inhibition of CTRP3 counteracted the function of C3G by promoting NRCM hyperplasia and inflammation. CONCLUSIONS: The results of the current study showed that the activation of CTRP3 contributed to the anti-hypertrophy effects of C3G.

A deep learning model to identify the fluid overload status in critically ill patients based on chest X-ray images.

INTRODUCTION: Recent studies have highlighted adverse outcomes of fluid overload in critically ill patients. Therefore, its early recognition is essential for the management of these patients. OBJECTIVES: Our aim was to propose a deep learning (DL) model using data from noninvasive chest X­ray (CXR) imaging associated with the fluid overload status. PATIENTS AND METHODS: We collected data from the Medical Information Mart for Intensive Care IV (MIMIC­IV, v. 1.0) and MIMIC Chest X­Ray (v. 2.0.0) databases for modeling, and from our hospital database for testing. The extravascular lung water index (ELWI) greater than 10 ml/kg and the global end-diastolic volume index (GEDI) greater than 700 ml/m2 were used as threshold values for the fluid overload status. A DL model with a transfer learning strategy was proposed to predict the fluid overload status based on CXR images, and compared with clinical and semantic label models. Additionally, a visualization technique was adopted to determine the important areas of features in the input images. RESULTS: The DL model showed a relatively strong performance for predicting the ELWI (area under the curve [AUC] = 0.896; 95% CI, 0.819-0.972 and AUC = 0.718; 95% CI, 0.594-0.822, respectively) and the GEDI status (AUC = 0.814; 95% CI, 0.699-0.930 and AUC = 0.649; 95% CI, 0.510-0.787, respectively) in both the primary and the test cohort. The performance was better than that of the clinical and semantic label models. CONCLUSIONS: As CXR is routinely used in the intensive care unit, a simple, fast, low­cost, and noninvasive DL model based on this modality can be regarded as an effective supplementary tool for identifying fluid overload, and should be widely adopted in the clinical setting, especially when invasive hemodynamic monitoring is not available.

ATP-binding cassette transporter A1 R219K polymorphism and coronary artery disease in Chinese population: a meta-analysis of 5,388 participants.

The ATP-binding cassette transporter A1 (ABCA1) R219K gene polymorphism has been suggested to lower the risk of coronary artery disease (CAD). However, research results remain debatable. Meta-analysis involving 2,730 CAD patients and 2,658 controls was performed to investigate the relationship between ABCA1 R219K gene polymorphism and CAD in Chinese population. A total of 14 studies which were obtained from electronic databases were analyzed. The pooled odds ratios (ORs) and their corresponding 95 % confidence intervals (95 % CIs) were estimated by a random effect model. A significant association between ABCA1 R219K gene polymorphism and CAD was found in the Chinese population under the following genetic models: an allelic genetic model (OR 0.70, 95 % CI 0.62-0.78, P < 0.00001), a recessive genetic model (OR 0.51, 95 % CI 0.41-0.64, P < 0.00001), an additive genetic model (OR 0.816, 95 % CI 0780-0.855, P = 0), a dominant genetic model (OR 1.326, 95 % CI 1.232-1.427, P = 0), a homozygote genetic model (OR 0.640, 95 % CI 0.575-0.712, P = 0), and a heterozygote genetic model (OR 0.640, 95 % CI 0.575-0.712, P = 0). The K allele of the ABCA1 R219K gene has a protective role for CAD risk in Chinese population and is possibly associated with decreased CAD susceptibility.

Inhibition of experimental myopia by a dopamine agonist: different effectiveness between form deprivation and hyperopic defocus in guinea pigs.

PURPOSE: The dopamine (DA) system in the retina is critical to normal visual development as lack of retinal DA signaling may contribute to myopic development. The involvement of DA in myopic development is complex and may be different between form deprivation and hyperopic defocus. This study evaluated effects of a non-selective DA receptor agonist, apomorphine (APO) on refractive development in guinea pigs treated with form deprivation or hyperopic defocus. METHODS: APO was subconjunctivally injected daily for 11 days in form-deprived (0.025 to 2.5 ng/µl) and defocused (0.025 to 250 ng/µl) eyes. Changes in ocular biometry and retinal concentration of DA and its metabolites (DOPAC) were measured in the 2 animal models to assess the level of DA involvement in each of the models (the less the change, the lower the involvement). RESULTS: Similar myopic degree was induced in both the deprived and defocused eyes (-4.06 D versus -3.64 D) at 11 days of the experiment. DA and DOPAC levels were reduced in the deprived eyes but did not change significantly in the defocused eyes compared to the fellow and normal control eyes. A subconjunctival injection of APO daily for 11 days at concentrations ranged from 0.025 to 2.5 ng/µl inhibited form deprivation myopia in a concentration-dependent manner. By contrast, the APO treatment ranged from 0.025 to 250 ng/µl did not effectively inhibit the defocus-induced myopia and the associated axial elongation. CONCLUSIONS: DA signaling may play a more critical role in form deprivation myopia than in defocus-induced myopia, raising a question whether the mechanisms of DA signaling are different under these two types of experimental myopia.

Regulation of angiotensin-(1-7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure.

AIM: To investigate the possible effects of telmisartan and losartan on cardiac function in adriamycin (ADR)-induced heart failure in rats, and to explore the changes in plasma level of angiotensin-(1-7)[Ang-(1-7)] and myocardial expression of angiotensin II type 1/2 receptors (AT(1)R / AT(2)R) and Mas receptor caused by the two drugs. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups: the control group, ADR-treated heart failure group (ADR-HF), telmisartan plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR). ADR was administrated (2.5 mg/kg, ip, 6 times in 2 weeks). The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (30 mg/kg daily), respectively, for 6 weeks. The plasma level of Ang-(1-7) was determined using ELISA. The mRNA and protein expression of myocardial Mas receptor, AT(1)R and AT(2)R were measured using RT-PCR and Western blotting, respectively. RESULTS: ADR significantly reduced the plasma level of Ang-(1-7) and the expression of myocardial Mas receptor and myocardial AT(2)R, while significantly increased the expression of myocardial AT(1)R. Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and suppressed myocardial AT(1)R expression, but did not influence the expression of Mas receptor and AT(2)R. CONCLUSION: The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1-7) and myocardial AT(1)R expression.

Early Fresh Frozen Plasma Transfusion: Is It Associated With Improved Outcomes of Patients With Sepsis?

Background: So far, no study has investigated the effects of plasma transfusion in the patients with sepsis, especially in the terms of prognosis. Therefore, we aimed to explore the association of early fresh frozen plasma (FFP) transfusion with the outcomes of patients with sepsis. Methods: We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care III database (v1.4). External validation was obtained from the First Affiliated Hospital of Wenzhou Medical University, China. We adopted the Sepsis-3 criteria to extract the patients with sepsis and septic shock. The occurrence of transfusion during the first 3-days of intensive care unit (ICU) stay was regarded as early FFP transfusion. The primary outcome was 28-day mortality. We assessed the association of early FFP transfusion with the patient outcomes using a Cox regression analysis. Furthermore, we performed the sensitivity analysis, subset analysis, and external validation to verify the true strength of the results. Results: After adjusting for the covariates in the three models, respectively, the significantly higher risk of death in the FFP transfusion group at 28-days [e.g., Model 2: hazard ratio (HR) = 1.361, P = 0.018, 95% CI = 1.054-1.756] and 90-days (e.g., Model 2: HR = 1.368, P = 0.005, 95% CI = 1.099-1.704) remained distinct. Contrarily, the mortality increased significantly with the increase of FFP transfusion volume. The outcomes of the patients with sepsis with hypocoagulable state after early FFP transfusion were not significantly improved. Similar results can also be found in the subset analysis of the septic shock cohort. The results of external validation exhibited good consistency. Conclusions: Our study provides a new understanding of the rationale and effectiveness of FFP transfusion for the patients with sepsis. After recognizing the evidence of risk-benefit and cost-benefit, it is important to reduce the inappropriate use of FFP and avoid unnecessary adverse transfusion reactions.

Fine-Needle Aspiration Biopsy of Intraocular Mass-Like Lesions.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance of fine-needle aspiration (FNA) biopsy for intraocular mass-like lesions and its contributing factors. METHODS: Intraocular FNA cases were retrieved and reviewed along with histopathologic follow-ups, if available. The effects of rapid on-site evaluation (ROSE), repeated biopsy, and adjunct immunocytochemical studies on cytologic diagnoses were analyzed. RESULTS: Of 72 FNA biopsies from 63 patients, nondiagnostic biopsy was seen in 17 cases (24%), whereas a definitive diagnosis was rendered in 39 cases (54%). The cytologic diagnoses correlated well with histopathologic follow-ups with a concordance rate of 61%. Almost all nondiagnostic biopsies (16/17, 94%) were seen in cases in which ROSE was not performed. Of the 7 patients in whom biopsy was repeated, a definitive diagnosis was rendered in 4 cases (57%). Immunocytochemistry was performed in the majority of cases with a malignant diagnosis, especially in metastatic tumors (75%). CONCLUSIONS: Our data demonstrates that FNA is an effective tool for the diagnosis of intraocular tumors. ROSE, repeated biopsy, and adjunct immunocytochemistry can help reduce the nondiagnostic rate and/or enhance diagnosis of malignancy, further improving FNA diagnostic performance.

An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study.

INTRODUCTION: So far, no study has investigated the association between subclinical hepatic fibrosis and sepsis, especially in terms of prognosis. OBJECTIVES: The purpose of our study was to explore the association of liver fibrosis indexes with the outcomes of septic patients without overt chronic liver disease. PATIENTS AND METHODS: We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care III (version 1.4) database. External validation was obtained from the First Affiliated Hospital of Wenzhou Medical University, China. We calculated the Aspartate Aminotransferase-to-Platelet Ratio Index, the Fibrosis­4 (FIB­4) score, and the Nonalcoholic Fatty Liver Disease Fibrosis Score using the existing formulas. The primary outcome was 28­day mortality. We assessed the associations of these 3 indexes with patient outcomes using logistic regression analysis. RESULTS: In the FIB­4 sepsis cohort (n = 1560), there was a significant stepwise increase from quartile 1 to quartile 4 in the risk of 28­day mortality (quartile 1: reference; quartile 2: odds ratio [OR], 1.57, P = 0.06, 95% CI, 0.98-2.515; quartile 3: OR, 2.363, P <0.001, 95% CI, 1.512-3.692; quartile 4: OR, 2.933, P <0.001, 95% CI, 1.895-4.538). The results of multivariable regression, Kaplan-Meier, and Cox regression analyses as well as external validation exhibited good consistency. CONCLUSIONS: The FIB­4 index is associated with 28­day, 90­day, and in­hospital mortality as well as with renal replacement therapy in septic patients without overt chronic liver disease. In other words, an advanced stage of subclinical hepatic fibrosis as represented by the FIB­4 score indicates poor outcomes in patients with sepsis.

Predictive models for patients with lung carcinomas to identify EGFR mutation status via an artificial neural network based on multiple clinical information.

PURPOSE: Epidermal growth factor receptor (EGFR) mutation testing has several limitations. Therefore, we built predictive models to determine the EGFR mutation status of patients and guide therapeutic decision-making. METHODS: We collected data from 320 patients with lung carcinoma, including sex, age, smoking history, serum tumour marker levels, maximum standardized uptake value, pathological results, computed tomography images, and EGFR mutation status. Artificial neural network (ANN) models based on multiple clinical characteristics were proposed to predict EGFR mutation status. RESULTS: A training set (n = 200) was used to develop predictive models of the EGFR mutation status (Model 1: area under the receiver operating characteristic curve [AUROC] = 0.910, 95% CI 0.861-0.945; Model 2: AUROC = 0.859, 95% CI 0.803-0.904; Model 3: AUROC = 0.711, 95% CI 0.643-0.773). A testing set (n = 50) and temporal validation data set (n = 70) were used to evaluate the generalisation performance of the established models (testing set: Model 1, AUROC = 0.845, 95% CI 0.715-0.932; Model 2, AUROC = 0.882, 95% CI 0.759-0.956; Model 3, AUROC = 0.817, 95% CI 0.682-0.912; temporal validation dataset: Model 1, AUROC = 0.909, 95% CI 0.816-0.964; Model 2, AUROC = 0.855, 95% CI 0.751-0.928; Model 3, AUROC = 0.831, 95% CI 0.723-0.910). The predictive abilities of the three ANN models were superior to that of a previous logistic regression model (P < 0.001, 0.027, and 0.050, respectively). CONCLUSIONS: ANN models provide a non-invasive and readily available method for EGFR mutation status prediction.

Conjunctival myxoid stromal tumour: a distinctive clinicopathological and immunohistochemical study.

BACKGROUND/AIMS: To describe the clinicopathological and immunohistochemical characteristics of 10 patients representing a new entity of benign conjunctival myxoid stromal tumours. METHODS: Retrospective review of clinical findings, histopathological and immunohistochemical studies identified 10 cases of low-grade conjunctival myxoid stromal tumours. Specimens were routinely processed and stained with H&E. Immunohistochemical stains for CD34, CD68, vimentin, S100, smooth muscle actin (SMA), myosin, desmin, actin, Bcl-2 and Ki-67 were performed. Specific stains for Alcian-blue periodic acid-Schiff (AB-PAS) and aldehyde fuchsin stains were also performed. RESULTS: Ten patients with an average age of 45.6±11.1 years had a tender white or faint yellow to red mass on the bulbar conjunctiva. All the lesions were completely removed, and none of the patients relapsed. Histologically, all neoplasms consisted of spindle-shaped cells that showed signs of pseudonuclear inclusions, multinuclear cells and had no atypia. The stroma consisted of a large amount of mucus and was infiltrated with delicate to ropey collagens, a few mast cells and new vessels. Immunohistochemical stains were positive for CD34, vimentin and Bcl-2; partial positive for CD68; very low for Ki-67; and negative for S100, SMA, myosin, desmin and actin. AB-PAS suggested that the stroma was mucinous. CONCLUSIONS: These rare benign mesenchymal conjunctival tumours are mostly unilateral and occur in the bulbar conjunctiva. Complete resection is the radical treatment. These lesions are characterised by multiple spindle cells, a large amount of mucus, and sharing similar basic histopathological features with conjunctival myxoma and conjunctival stromal tumour. We suggest naming these lesions 'conjunctival myxoid stromal tumours'.

EGFR-TKI-sensitive mutations in lung carcinomas: are they related to clinical features and CT findings?

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation testing is restricted to several limitations. In this study, we examined the relationship between EGFR mutation status and clinicoradiological characteristics in a Chinese cohort of patients. MATERIALS AND METHODS: The data of patients who were diagnosed with lung carcinoma and underwent both EGFR testing and chest computed tomography (CT) at our hospital between January 1, 2011, and November 31, 2015, were retrospectively analyzed. The age, sex, and smoking index of the patients, the size, margin, and density of the tumor, and the presence of specific signs visible on the CT images were assessed. RESULTS: The results showed a higher rate of EGFR-tyrosine kinase inhibitor (TKI)-sensitive group than nonsensitive group in female patients and patients with a low smoking index (P<0.001, both). In logistic regression analyses, tumor size (P<0.001), smooth margins (P=0.015), and angular margins (P<0.001) were independent negative predictors of EGFR-TKI-sensitive group. Pleural indentation (P<0.001) and air bronchogram (P=0.025) were independent positive predictors of EGFR-TKI-sensitive group. Patients with squamous cell carcinoma had fewer sensitive mutations than those with either adenocarcinoma (P<0.001) or adenosquamous carcinoma (P<0.001). CONCLUSION: Clinical and CT characteristics differed significantly between EGFR-TKI-sensitive and nonsensitive groups. Our findings may be useful in deciding therapeutic strategies for patients in whom EGFR testing is not possible.

Plasma vascular non-inflammatory molecule 3 is associated with gastrointestinal acute graft-versus-host disease in mice.

BACKGROUND: Gastrointestinal acute graft-versus-host disease (GI aGVHD) is a lethal complication following allogeneic hematopoietic stem cell transplantation (HSCT). However, it is still very difficult to make a diagnosis of GI aGVHD in practice. To date, no consensus plasma biomarker of GI aGVHD can be used to help make a diagnosis. Here, we attempted to identify GI aGVHD associated plasma proteins in murine model, which can help make a diagnosis of GI aGVHD. METHODS: We used 8-plex isobaric tags for relative and absolute quantitation (8-plex iTRAQ) to screen out proteins in plasma samples taken from murine models before and after allogeneic HSCT. Next mRNA expressions were validated by quantitative real-time polymerase chain reaction in mouse intestinal epithelial samples. RESULTS: We found that five proteins were increased at least 2-fold in the allogeneic group at day 7 compared with days 0, 3 and 15 (after Cyclosporin A treatment) and the syngeneic group at day 7. These 5 proteins were VNN3, ZNF746, C4BP, KNG1 and FETUB, and they were consistent with results from negative labeling with 8-plex iTRAQ. Furthermore, increase in mRNA level of VNN3 was confirmed in murine intestinal epithelial samples with aGVHD. CONCLUSIONS: Our results demonstrate that plasma VNN3 protein is associated with GI aGVHD in murine model.

Epibulbar complex cartilaginous choristoma: A distinctive clinicopathological case series and literature review.

To newly describe the clinical and histopathological characteristics of epibulbar complex cartilaginous choristoma incidentally observed in a series of pterygium excision patients.Noncomparative case series with chart review of 8 patients.During a 4-year period, we identified 8 cases of conventional unilateral nasal subpterygial cartilaginous choristoma in 1799 pterygium patients and analyzed their clinicopathological features. The incidence rate of this entity is 0.44% in pterygium patients. All of the cartilaginous choristomas were buried deep in the caruncle, covered by the pterygium, and embedded in tenon facia tissue. Its clinicopathological characteristics include hyaline cartilaginous tissue that is surrounded by fibrous connective tissue and smooth muscle bundles. S-100 protein-staining specifically revealed chondrocytes embedded within chondroid matrix.Epibulbar complex cartilaginous choristoma covered by pterygia and predominantly observed in the older population is rare. The lesions were buried deep in the caruncle, covered by the pterygium and embedded in tenon fascia tissue. These findings are inconsistent with those in previous reports.

Clinical features and surgical outcomes of primary canaliculitis with concretions.

The purpose of our study is to analyze the clinical, ultrasonic, microbiologic, and histopathologic characteristics, management, and outcomes in a series of primary canaliculitis with concretions patients who underwent canaliculotomy with curettage.Thirty-six patients were reviewed for age, sex, location and laterality, duration of symptoms, clinical symptoms, ultrasonic signs, result of microbiologic culture and histopathologic examination, treatment, and outcomes. Main outcomes were the clinical, ultrasonic, and microbiological characteristics of the canalicular concretions; the histopathologic profiles; and the treatment effect.Thirty-six patients were identified with concretions in all 37 cases of the patients with canaliculitis. There were 30 (83.3%) female patients with a mean age of 54.2 years. Twenty-eight (77.8%) patients were misdiagnosed or delayed diagnosed, and the mean duration was 17.1 months. The common most clinical presentations were discharge (100%), epiphora (66.7%), erythema (52.8%), and swelling (47.2%), and concretions were found in 31 of 37 patients by typical clinical manifestations and in 5 of 6 patients by ultrasonic. Actinomyces was found in 8 of 13 histopathologic specimens, and microbiological cultures were positive in 13 of 24 patients. All patients underwent canaliculotomy with curettage to completely remove all concretions and contents; 35 of 36 patients' symptoms improved and 1 recurred after treatment at a median of 21.7 months follow-up according to the telephonic questionnaires.Canalicular concretions play an important role in primary canaliculitis. Canaliculotomy with curettage is a standard therapy with canalicular concretions, and the surgical removal of all possible concretions is essential for cure.

B Lymphocyte Chemoattractant (CXCL13) Is an Indicator of Acute Gastrointestinal GVHD in Murine Model.

Gastrointestinal acute graft-vs.-host disease (GI aGVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation and is a major cause of morbidity and mortality. In addition, GI aGVHD is often clinically indistinguishable from other causes of GI dysfunction such as conditioning regimen toxicity, infections, or medications, which complicates the diagnosis. Thus, specific biomarkers are needed to help improve diagnosis and obtain a deeper understanding of the cytokine changes in GI aGVHD. An MHC-mismatched model of aGVHD was established by transplanting 1 × 107 bone marrow nuclear cells and 3 × 107 spleen cells from C57/Bl6 mice or from BALB/c mice into lethally irradiated BALB/c recipients. The mice in the allogeneic transplantation group were intraperitoneally treated with 20 mg kg-1 day-1 cyclosporin A after aGVHD developed. Five micrograms of lipopolysaccharide were administered intraperitoneally daily to syngeneic recipients at day 11 to imitate infection; the same volume of phosphate-buffered saline was administered to control mice. The mice were killed at the indicated time points. Forty molecules derived from the GI tract were screened cytokine array. The data demonstrated that the expression of B lymphocyte chemoattractant (CXCL13) was increased by ~10-, 12-, and 16-fold upon the occurrence of aGVHD compared with infection, aGVHD after treatment, and the syngeneic control group, respectively. Thus, the elevation of BLC (CXCL13) is an indicator of acute GI GVHD.

Toughening and its association with the postharvest quality of king oyster mushroom (Pleurotus eryngii) stored at low temperature.

Toughening-induced textural decay easily occurs in stored mushrooms. The objective of this study was to investigate the textural alteration caused by toughening in relation to other quality attributes of king oyster mushroom (Pleurotus eryngii). Fresh king oyster mushrooms, packed in low-density polyethylene bags, were stored at different low temperatures for 18 days to measure textural and other quality attributes. It was found that toughening occurred twice during the entire storage time. Highly associated change profiles were observed for the lignin content and activities of three important enzymes involved in lignin synthesis. The chitin and cellulose contents exhibited low correlation with toughening. Malondialdehyde content, electrolyte leakage rate and total phenolics content appeared to be related to toughening, but the browning index showed a negative correlation with toughening. Our results suggested that toughening may be mainly caused by lignification and can affect the postharvest quality of the tested mushrooms.

Safety of femtosecond laser-assisted cataract surgery: assessment of aqueous humour and lens capsule.

PURPOSE: To investigate the effect of femtosecond laser-assisted cataract surgery (FLACS) on aqueous humour and lens capsule. METHODS: This prospective randomized comparative study enrolled 19 eyes that underwent FLACS as the trial group and 20 eyes that underwent conventional phacoemulsification as the control group. The femtosecond laser platform (LLS-fs 3D; LensAR, Orlando, FL, USA) was used to generate capsulotomy (laser energy 8 µJ) and lens fragmentation (laser energy 10 µJ). Morphology of the cutting edge and cells of anterior capsule was assessed by light microscopy. The proteins in the aqueous humour were identified by mass spectrometry (Ultraflex III TOF/TOF; Bruker Dalton, Bremen, Germany). Electrolyte in the aqueous humour was detected by a chemistry analyzer (Aeroset Clinical Chemistry Analyzer; Abbott Laboratories, Abbott Park, IL, USA). RESULTS: The cutting edge of anterior capsule was saw-tooth-shaped under magnification of 200× and 400× in the trial group, while it was smooth in the control group. Intact cells were found in the boundary area next to the cutting edge of anterior capsule in both groups. ß-Crystallin B1, γ-crystallin S and transferrin were detected in the aqueous humour in the trial group. The concentrations of K+ , Na+ and Cl- in the aqueous humour in the trial group differed significantly from those in the control group (p = 0.02, 0.03 and 0.04, respectively). CONCLUSION: Femtosecond laser-assisted cataract surgery (FLACS) causes release of transferrin and crystallin from lens to aqueous humour and results in significant changes in the concentrations of K+ , Na+ and Cl- in aqueous humour. However, these changes due to FLACS have no clinical significance or toxicity.