Breaking the vitrification limitation of monatomic metals.

The question of whether all materials can solidify into the glassy form proposed by Turnbull half a century ago remains unsolved. Some of the simplest systems of monatomic metals have not been vitrified, especially the close-packed face-centred cubic metals. Here we report the vitrification of gold, which is notoriously difficult to be vitrified, and several similar close-packed face-centred cubic and hexagonal metals using a method of picosecond pulsed laser ablation in a liquid medium. The vitrification occurs through the rapid cooling during laser ablation and the inhibition of nucleation by the liquid medium. Using this method, a large number of atomic configurations, including glassy configurations, can be generated simultaneously, from which a stable glass state can be sampled. Simulations demonstrate that the favourable stability of monatomic metals stems from the strong topological frustration of icosahedra-like clusters. Our work breaks the limitation of the glass-forming ability of matter, indicating that vitrification is an intrinsic property of matter and providing a strategy for the preparation and design of metallic glasses from an atomic configuration perspective.

Observation of an isothermal glass transition in metallic glasses.

Glass transition, commonly manifested upon cooling a liquid, is continuous and cooling rate dependent. For decades, the thermodynamic basis in liquid-glass transition has been at the center of debate. Here, long-time isothermal annealing was conducted via molecular dynamics simulations for metallic glasses to explore the connection of physical aging in supercooled liquid and glassy states. An anomalous two-step aging is observed in various metallic glasses, exhibiting features of supercooled liquid dynamics in the first step and glassy dynamics in the second step, respectively. Furthermore, the transition potential energy is independent of initial states, proving that it is intrinsic for a metallic glass at a given temperature. We propose that the observed dynamic transition from supercooled liquid dynamics to glassy dynamics could be glass transition manifested isothermally. On this basis, glass transition is no longer cooling rate dependent, but is shown as a clear phase boundary in the temperature-energy phase diagram. Hence, a modified out-of-equilibrium phase diagram is proposed, providing new insights into the nature of glass transition.

A Review of the Extent of Pain Catastrophizing in Patients Who Have Undergone Total Knee Replacement.

OBJECTIVES: This study aimed to analyze the current status and influencing factors of pain catastrophizing in patients undergoing total knee replacement (TKR) and to provide a basis and reference for the clinical improvement of pain catastrophizing in these patients. DESIGN: This study was designed in accordance with PRISMA guidelines. DATA SOURCES: PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu and Chinese Biomedical Literature Databases. REVIEW/ANALYSIS METHODS: A scoping review was performed using PubMed, the Web of Science, the Elton B. Stephens Company, the Cochrane Library, Embase, Chinese National Knowledge Infrastructure, the WanFang, Weipu, and Chinese Biomedical Literature Databases, and after literature screening and data extraction, the results were summarized. RESULTS: A total of 23 articles were included in the study. Pain catastrophizing is mostly assessed using the Pain Catastrophizing Scale and the Coping Strategies Questionnaire. The level of pain catastrophizing is an independent predictor of pain in patients undergoing TKR and is influenced by demographic, psychological, co-morbid, and prognostic factors. Pain catastrophizing interventions mainly consist of surgery, physiotherapy, medication, and psychological therapy. CONCLUSIONS: Pain catastrophizing involves multiple factors, and it is necessary to explore the predictors affecting pain catastrophizing, improve the systematic evaluation of pain catastrophizing and adopt the appropriate intervention methods.

Data-driven discovery of a universal indicator for metallic glass forming ability.

Despite the importance of glass forming ability as a major alloy characteristic, it is poorly understood and its quantification has been experimentally laborious and computationally challenging. Here, we uncover that the glass forming ability of an alloy is represented in its amorphous structure far away from equilibrium, which can be exposed by conventional X-ray diffraction. Specifically, we fabricated roughly 5,700 alloys from 12 alloy systems and characterized the full-width at half-maximum, Δq, of the first diffraction peak in the X-ray diffraction pattern. A strong correlation between high glass forming ability and a large Δq was found. This correlation indicates that a large dispersion of structural units comprising the amorphous structure is the universal indicator for high metallic glass formation. When paired with combinatorial synthesis, the correlation enhances throughput by up to 100 times compared to today's state-of-the-art combinatorial methods and will facilitate the discovery of bulk metallic glasses.

A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma.

Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing nonanthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision making. Data from 722 patients with ENKTL from international centers were analyzed. A 7-SNP-based classifier was constructed using LASSO Cox regression in the training cohort (n = 336) and further validated in the internal testing cohort (n = 144) and in 2 external validation cohorts (n = 142 and n = 100). The 7-SNP-based classifier showed good prognostic predictive efficacy in the training cohort and the 3 validation cohorts. Patients with high- and low-risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all P < .001). The 7-SNP-based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. Application of the 7-SNP-based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significantly improved PFS and OS vs radiotherapy alone in high-risk Ann Arbor stage I patients, whereas there was no statistical difference between the 2 therapeutic modalities among low-risk patients. A nomogram was constructed comprising the classifier and clinicopathological variables; it showed remarkably better predictive accuracy than either variable alone. The 7-SNP-based classifier is a complement to existing risk-stratification systems in ENKTL, which could have significant implications for clinical decision making for patients with ENKTL.

Relationships among social support, coping style, self-stigma, and quality of life in patients with diabetic foot ulcer: A multicentre, cross-sectional study.

Patients with diabetic foot ulcer have a significantly lower quality of life. Quality of life could be connected to other psychological or social processes. The purpose of this study was to examine the relationships between social support, decision regret, self-stigma, and quality of life in patients with diabetic foot ulcers. The sample of the study consisted of 229 diabetic foot ulcer patients. Data were collected from September 2019 to March 2020. The demographic and clinical information, the Stigma Scale for Chronic Illness, Medical Coping Scale, Social Support Scale, and Quality of Life scale were used to assess the quality life for diabetic foot ulcer. Pearson correlation coefficient and structural equation modelling were used for data analysis. The quality of life was negatively correlated with self-stigma, positively correlated with social support, giving up coping, and not significantly correlated with confrontation coping and avoidance coping. Self-stigma has significant indirect effects on quality of life through social support and coping style. Further clinical intervention strategies for decreasing self-stigma as well as strengthening social support and positive coping styles are needed to inform diabetic foot ulcer patients, thus improving their quality of life.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Camrelizumab in different PD-L1 expression cohorts of pre-treated advanced or metastatic non-small cell lung cancer: a phase II study.

BACKGROUND: This phase II study evaluated camrelizumab in different PD-L1 expression cohorts of patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC; NCT03085069, registered March 21, 2017). METHODS: Patients who progressed during/after chemotherapy were enrolled and divided into four cohorts based on PD-L1 tumor proportion score (TPS). Patients with EGFR/ALK alterations and PD-L1 TPS ≥ 50% were also eligible. All enrolled patients received camrelizumab at 200 mg IV Q2W. The primary endpoint was objective response rate. RESULTS: A total of 146 patients were enrolled. As of data cutoff on Aug 20, 2020, the median follow-up was 29.5 months (95% CI 27.4-30.8). Objective response rate was 17.8% (95% CI 12.0-25.0) and improved with the increasing PD-L1 TPS (TPS < 1%, 12.2% [95% CI 5.7-21.8]; ≥ 1-< 25%, 19.4% [95% CI 7.5-37.5]; ≥ 25-< 50%, 36.4% [95% CI 10.9-69.2]; ≥ 50%, 23.3% [95% CI 9.9-42.3]). No response was observed in the five patients harboring EGFR mutations. Median progression-free survival was 3.2 months (95% CI 2.0-3.4), and patients with positive PD-L1 TPS had longer progression-free survival. Median overall survival was 14.8 months (95% CI 10.2-18.7). Treatment-related adverse events (TRAEs) of any grade occurred in 87.7% of patients, and 21.2% had grade ≥ 3 TRAEs. CONCLUSION: Camrelizumab showed improved efficacy compared with historical data of the second-line chemotherapy in pre-treated advanced/metastatic NSCLC. Patients with positive PD-L1 expression derived greater benefit from camrelizumab. Camrelizumab has a manageable safety profile.

A Case of Misdiagnosis Caused by the Coinheritance of Hb G-Siriraj [ß7(A4)Glu→Lys; HBB: c.22G>A] and Hb H Disease.

Despite the fact that most hemoglobin (Hb) variants are clinically and hematologically silent, they can interact with thalassemias, which could sometimes give rise to complicated routine thalassemia diagnostics. Hb G-Siriraj [ß7(A4)Glu→Lys; HBB: c.22G>A] alone is a benign condition, but its coinheritance with α-thalassemia (α-thal) may lead to misdiagnosis. We describe the case of a Chinese woman with an elevated Hb A2 level who was assumed to carry heterozygous ß-thalassemia (ß-thal), but was later shown to be a double heterozygote for Hb G-Siriraj and Hb H disease. This study for the first time described hematological characteristics of a patient with a double heterozygosity for Hb G-Siriraj and Hb H disease. It is of great significance for technicians and clinicians to expand their knowledge as well as to help guide clinical diagnosis, population screening and genetic counseling.

[Latest Research Findings on the Role of Non-Tumor Cells in Glioma Microenvironment].

As the tumor cell-centered treatment strategies cannot curb the malignant progression of glioblastoma effectively, the therapeutic effect of glioblastoma is still not satisfactory. In addition to glioma cells, glioma microenvironment (GME) comprises massive numbers of non-tumor cells and soluble cytokines. The non-tumor cells include endothelial cells, pericytes, microglia/macrophages, mesenchymal cells, astrocytes, neurons, etc. These non-tumor cell components, together with glioma cells, form one organism which regulates the progression of glioma. Considerable progress has been been in research on GME, which will be conducive to the development of non-tumor cell targeted therapies and and improvements in the prognosis of glioma patients. Herein, we summarized the interaction of glioma cells with endothelial cells, pericytes, microglia/macrophages, astrocytes, neurons and mesenchymal cells, a topic that has been extensively researched, as well as the corresponding translational studies. We also discussed the potential challenges and opportunities of developing glioma treatments based on tumor microenvironment.

[Development and Evaluation of Prognostic Nomogram Model for Adult Ventricle Glioma Patients].

Objective: To explore the prognostic factors of adult ventricle glioma (AVG) and to construct and evaluate a survival-related prognostic nomogram model, which could provide further reference for the clinical management of AVG patients. Methods: The patients covered in the study were selected from the Surveillance Epidemiology and End Results (SEER) database (1973-2016). They all had definite histological diagnosis of AVG. They were assigned randomly to the training cohort and the validation cohort by random number table at a 2/1 ratio. Survival analysis was performed by Kaplan-Meier analysis. Cox regression analysis was employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Then, integrating the basic characteristics of patients, the survival-related nomogram predictive model for OS and CSS in the training cohort was constructed, respectively. After that, internal cross validation and external validation of the model were carried out with the training cohort and the validation cohort in succession. The authenticity and reliability of the nomogram model were evaluated by calculating the concordance index (C-index). Calibration plots were constructed to assess the agreement between the predicted values and the observed values in the training cohort and the validation cohort. Results: A total of 369 AVG patients, including 218 males and 151 females, were included. The median age of the patients was 53. According to the WHO classification of gliomas, 66 (17.9%) patients had grade Ⅱ gliomas, 73 (19.8%) had grade Ⅲ gliomas, and 230 (62.3%) had grade Ⅳ gliomas. Regarding the extent of resection (EOR), 59 (16.0%) had gross total resection (GTR) and 145 (39.3%) had subtotal resection (STR) or partial resection (PR). Of all the patients, 167 (45.3%) received postoperative radiotherapy and 143 (38.8%) received postoperative chemotherapy. Patients were randomized into the training cohort ( n=246) and the validation cohort ( n=123), and there was no significant difference ( P>0.05) in the basic clinical characteristics between the training cohort and the validation cohort. In the training cohort, Cox regression analysis revealed that the independent prognostic factors for OS and CSS included age≥65, grades Ⅲ and Ⅳ according to the WHO classification of gliomas, and not receiving radiotherapy. Furthermore, 5 variables, including age, gender, WHO grades, surgery, and radiotherapy, were used to construct the nomogram model for predicting 6-month, 1-year, and 2-year OS and CSS. The results of internal cross validation in the training cohort showed that the C-indexes of OS and CSS were 0.758 and 0.765, respectively. The external validation results of the validation cohort showed that the C-indexes of OS and CSS were 0.733 and 0.719, respectively. Calibration plots for 6-month, 1-year, and 2-year OS in the training cohort showed relatively good agreement, while in the validation cohort the agreement was relatively low. The 6-month, 1-year, and 2-year CSS calibration plots had results similar to the calibration plots of OS. Conclusion: This nomogram predictive model of OS and CSS showed moderately reliable predictive performance, providing helpful reference information for clinicians to make quick and simple assessment of the survival probability of AVG patients.

Effect of hypertensive disorders of pregnancy on peripheral venous blood cell count in preterm infants with a gestational age of 28-34 weeks. / å¦Šå¨ æœŸé«˜è¡€åŽ‹ç–¾ç— å¯¹èƒŽé¾„28~34周早产儿外周静脉血细胞计数的影响.

OBJECTIVES: To study the effect of hypertensive disorders of pregnancy on peripheral venous blood cell count in preterm infants with a gestational age of 28-34 weeks. METHODS: A total of 227 preterm infants with a gestational age of 28-34 weeks who were admitted to the Department of Pediatrics, the First Hospital Affiliated to Kunming Medical University, from January to December 2020, and whose mothers had hypertensive disorders of pregnancy were enrolled as the study group. A total of 227 preterm infants with a gestational age of 28-34 weeks who were admitted during the same period and whose mothers did not have hypertensive disorders of pregnancy were enrolled as the control group. According to maternal blood pressure during pregnancy, the study group was divided into three subgroups: gestational hypertension (n=75), mild preeclampsia (n=81), and severe preeclampsia (n=71). According to the birth weight of the preterm infants, the study group was divided into two subgroups: small for gestational age (SGA) (n=113) and appropriate for gestational age (AGA) (n=114). Peripheral blood cell count on day 1 after birth was compared between the study and control groups, as well as between the subgroups of the study group. RESULTS: Compared with the control group, the study group had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count (P<0.05) and significantly higher incidence rates of leucopenia and neutropenia (P<0.05). The subgroup analysis showed that the mild preeclampsia and severe preeclampsia subgroups had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count than the gestational hypertension subgroup (P<0.05), and that the SGA subgroup had significantly lower white blood cell count, absolute neutrophil count, and blood platelet count than the AGA subgroup (P<0.05). CONCLUSIONS: Hypertensive disorders of pregnancy can affect the peripheral venous blood cell count of preterm infants, which is more significant in infants with maternal preeclampsia and SGA infants.

A Novel Hemoglobin Variant Hb Liaobu [α107(G14)Val→Leu, HBA2: c.322G>C] Detected by Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry.

We here describe a novel hemoglobin (Hb) variant, Hb Liaobu [α107(G14)Val→Leu, HBA2: c.322G>C], in a Chinese family. The structurally abnormal α chain variant could not be detected using capillary electrophoresis (CE) and was subsequently characterized by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS), and further confirmed by reversed phase high performance liquid chromatography (HPLC). Sanger sequencing revealed a novel base mutation on the α2-globin gene and RNA analysis by reverse transcription polymerase chain reaction (RT-PCR) showed the presence of an abnormal HBA transcript. The isopropanol stability test indicated the stable state of this structural Hb variant. In conclusion, a new Hb variant, Hb Liaobu, was discovered and characterized. It was proven to be a nonpathogenic variant. Our study resolved the confusion in the clinical diagnosis of individuals with this novel Hb variant in this family.

Targeted Host Cell Protein Quantification by LC-MRM Enables Biologics Processing and Product Characterization.

Multiple reaction monitoring (MRM) is a liquid chromatography-mass spectrometry (LC-MS) based quantification platform with high sensitivity, specificity, and throughput. It is extensively used across the pharmaceutical industry for the quantitative analysis of therapeutic molecules. The potential of MRM analysis for the quantification of specific host cell proteins (HCPs) in bioprocess, however, has yet to be well established. In this work, we introduce a multiplex LC-MRM assay that simultaneously monitors two high risk lipases known to impact biologics product quality, Phospholipase B-like 2 protein (PLBL2) and Group XV lysosomal phospholipase A2 (LPLA2). Quantitative data generated from the LC-MRM assay were used to monitor the clearance of these lipases during biologics process development. The method is linear over a dynamic range of 1 to 500 ng/mg. To demonstrate the fitness for use and robustness of this assay, we evaluate a comprehensive method qualification package that includes intra- and inter-run precision and accuracy across all evaluated concentrations, selectivity, recovery and matrix effect, dilution linearity, and carryover. Additionally, we illustrate that this assay provides a rapid and accurate means of monitoring high risk HCP clearance for in-process support and can actively guide process improvement and optimization. Lastly, we compare direct digestion platforms and affinity depletion platforms to demonstrate the impact of HCP-mAb interaction on lipase quantification.

Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma.

Mature T-cell lymphomas, including peripheral T-cell lymphoma (PTCL) and extranodal NK/T-cell lymphoma (NKTL), represent a heterogeneous group of non-Hodgkin lymphomas with dismal outcomes and limited treatment options. To determine the extent of involvement of the JAK/STAT pathway in this malignancy, we performed targeted capture sequencing of 188 genes in this pathway in 171 PTCL and NKTL cases. A total of 272 nonsynonymous somatic mutations in 101 genes were identified in 73% of the samples, including 258 single-nucleotide variants and 14 insertions or deletions. Recurrent mutations were most frequently located in STAT3 and TP53 (15%), followed by JAK3 and JAK1 (6%) and SOCS1 (4%). A high prevalence of STAT3 mutation (21%) was observed specifically in NKTL. Novel STAT3 mutations (p.D427H, E616G, p.E616K, and p.E696K) were shown to increase STAT3 phosphorylation and transcriptional activity of STAT3 in the absence of cytokine, in which p.E616K induced programmed cell death-ligand 1 (PD-L1) expression by robust binding of activated STAT3 to the PD-L1 gene promoter. Consistent with these findings, PD-L1 was overexpressed in NKTL cell lines harboring hotspot STAT3 mutations, and similar findings were observed by the overexpression of p.E616K and p.E616G in the STAT3 wild-type NKTL cell line. Conversely, STAT3 silencing and inhibition decreased PD-L1 expression in STAT3 mutant NKTL cell lines. In NKTL tumors, STAT3 activation correlated significantly with PD-L1 expression. We demonstrated that STAT3 activation confers high PD-L1 expression, which may promote tumor immune evasion. The combination of PD-1/PD-L1 antibodies and STAT3 inhibitors might be a promising therapeutic approach for NKTL, and possibly PTCL.

Short report: relationships among resilience, social support, coping style and posttraumatic growth in hematopoietic stem cell transplantation caregivers.

Posttraumatic growth has become a focus of concern in cancer caregivers, but a few studies have explored relationships among resilience, social support, coping style, and posttraumatic growth, especially in hematopoietic stem cell transplantation caregivers. A descriptive cross-sectional survey was conducted. Three hundred and fourteen participants completed questionnaires consisting of demographics, Posttraumatic Growth Inventory, Perceived Social Support Scale, Connor-Davidson Resilience Scale 10 and Coping Style Questionnaire. Pearson correlation analyses revealed that posttraumatic growth was positively associated with resilience, social support, and positive coping style, while, passive coping style was negatively associated with posttraumatic growth. At the same time, structural equation modeling analyses showed that resilience mediated the relationship between positive coping style and posttraumatic growth. Positive coping style and resilience played completely intermediary role between social support and posttraumatic growth.

Selective Tryptophan Oxidation of Monoclonal Antibodies: Oxidative Stress and Modeling Prediction.

Oxidation of tryptophan not only generates heterogeneity of a therapeutic monoclonal antibody (mAb) but also can be a potential critical quality attribute (CQA) of the product. In this study, mAbs A-C of IgG1 and IgG4 (immunoglobulin G, IgG) isotypes with oxidized tryptophan (Trp) residues were selectively generated by incubating the mAbs with 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) in formulations containing l-methionine. The site-specific oxidation of tryptophan residues were confirmed by liquid chromatography coupled with mass spectrometry (LC-MS) studies. The site of oxidation was identified to be a conserved tryptophan residue in the heavy chain complementarity determining region 3 (CDR3) of mAbs A and B with no significant oxidation found on other tryptophan residues including those in close proximity to CDR3. For mAb C, all tryptophan residues including one in the heavy chain CDR1 and a tryptophan in close proximity to heavy chain CDR3 were not susceptible to oxidation. For all three mAbs, the structure and tryptophan oxidation relationship was further studied by computational modeling of the variable domain of the antibodies (variable fragment, Fv). The computational modeling provided a structural understanding at the molecular level to the tryptophan oxidation, where high solvent accessibility is a prerequisite for heavy chain CDR3 tryptophan oxidation. However, higher oxidation susceptibility of tryptophan in heavy chain CDR3 did not linearly correlate to higher solvent accessibility, suggesting that other factors including side-chain orientation and/or surrounding structure elements around the heavy chain CDR3 may also be involved. Through this study, we demonstrate that a selective oxidation system, together with computational modeling, can be an important tool to identify potential CQAs of a therapeutic mAb such as tryptophan oxidation liabilities during the mAb's development.

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation. METHODS: We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing. RESULTS: Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines. CONCLUSIONS: The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

Molecular and Hematological Characterization of a Novel Translation Initiation Codon Mutation of the α2-Globin Gene (ATG>ATC or HBA2: c.3G>C).

Although mutations causing α-thalassemia (α-thal) are mainly larger deletions involving one or both of the duplicated α-globin genes, point mutations are not rare. We have identified a novel mutation of the translation initiation codon of the α2-globin gene with DNA sequencing and allele-specific multiplex ligation-dependent probe amplification (MLPA) in a Chinese family. RNA analysis was performed with reverse transcription-MLPA (RT-MLPA). A novel mutation at the translation initiation codon of the α2-globin gene (HBA2: c.3G>C) was identified. The proband and his father, who were both carriers of this mutation, had a hematological phenotype of mild α+-thalassemia (α+-thal) trait with low-normal limit of mean corpuscular volume (MCV) and normal Hb A2. RNA analysis showed markedly decreased levels of α-globin mRNA and the presence of a small amount of mutant mRNA. The HBA2: c.3G>C mutation most likely caused α-thal by lowering levels of wild α-globin chain. Our study increases the mutation spectrum of α-thal.

TIPE2 attenuates liver fibrosis by reversing the activated hepatic stellate cells.

TIPE2, the tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TNFAIP8L2), plays an important role in regulating inflammation and immune homeostasis. Recent studies discovered that TIPE-2 involved in the development of several tumors and other proliferative diseases. The purpose of this study was to explore the function of TIPE-2 in the activation and proliferation in HSC-T6 cells. Our study showed low expression of TIPE-2 in primary HSCs from CCl4-treated mice and activated HSC-T6 cells. Functionally, over-expression of TIPE-2 by GV141-TIPE-2 hindered the HSC-T6 cells activation and proliferation and expressions of ß-Catenin, Cmyc, Cyclin D1. However, inhibition TIPE-2 expression by TIPE-2 siRNA showed the opposite effect. These observations revealed that TIPE-2 held a protective effect on liver fibrosis and could be a potential therapeutic target.