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关键词： Schizophrenia   Bipolar disorder   Major depressive disorder   Postmortem   Astrocytes   Microglia   Oligodendrocytes   FIBRILLARY ACIDIC PROTEIN   DORSOLATERAL PREFRONTAL CORTEX   ANTERIOR CINGULATE CORTEX   MESSENGER-RNA LEVELS   WHITE-MATTER   DEPRESSIVE-DISORDER   BIPOLAR-DISORDER   GENE-EXPRESSION   SOMAL SIZE   HLA-DR  

摘要： There have been a large number of reports about glial cell dysfunction being related to major psychiatric diseases such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). In this review, we provide an overview of postmortem studies analyzing the structural changes of glial cells in these three major psychiatric diseases, including the density, number and size of glial cells, and the expression of related markers. Up to May 1, 2021, 108 articles that met the inclusion criteria were identified by searching PubMed and Web of Science. Although most studies evaluating total glial cells did not show abnormalities in the brains of postmortem patients, astrocytes, microglial cells, and oligodendrocytes seem to have specific patterns of changes in each disease. For example, out of 20 studies that evaluated astrocyte markers in MDD, 11 studies found decreased astrocyte marker expression in MDD patients. Similarly, out of 25 studies evaluating oligodendrocyte markers in SCZ, 15 studies showed decreased expression of oligodendrocyte markers in different brain regions of SCZ patients. In addition, activated microglial cells were observed in patients with SCZ, BD, and MDD, but suicide may be a confounding factor for the observed effects. Although the data from the included studies were heterogeneous and this cannot be fully explained at present, it is likely that there are a variety of contributing factors, including the measured brain regions, methods of measurement, gender, age at time of death, and medications.

关键词： Repeat-dose   Cigarette   e-cigarette   Airway   Transcriptome   SMOKE   TOBACCO   ABCB6  

摘要： Cigarette smoke deregulates several biological pathways by modulating gene expression in airway epithelial cells and altering the physiology of the airway epithelium. The effects of repeated exposures of electronic cigarette delivery systems (ENDS) on gene expression in airway epithelium are relatively unknown. In order to assess the effect of repeated exposures of ENDS, primary normal human bronchial epithelial (NHBE) cells grown at air-liquid interface (ALI) were exposed to cigarette and ENDS preparations daily for 10 days. Cigarette smoke preparations significantly altered gene expression in a dose-dependent manner compared to vehicle control, including genes linked to oxidative stress, xenobiotic metabolism, cancer pathways, epithelial-mesenchymal transition, fatty acid metabolism, degradation of collagen and extracellular matrix, O-glycosylation, and chemokines/cytokines, which are known pathways found to be altered in smokers. Conversely, ENDS preparations had minimal effect on transcriptional pathways. This study revealed that a sub-chronic exposure of primary NHBE cultures to cigarette and ENDS preparations differentially regulated genes and canonical pathways, with minimal effect observed with ENDS preparations compared to cigarette preparations. This study also demonstrates the versatility of primary NHBE cultures at ALI to evaluate repeat-dose exposures of tobacco products.

关键词： X80 pipeline steel   Room temperature creep   Dislocation density   Molecular dynamics simulation   FAILURE   DEFORMATION   BEHAVIOR   CRACK  

摘要： Gas transformation field recognized that X80 pipeline steel would fail in operation occasionally some days after pressure stabilized, commonly referred to as a time-delayed failure. Standard creep test usually presents an average and macrostructure results, but understand creep behavior at crystal size level is still interesting. This paper presents the analysis results of the primary creep behavior at dislocation evolution under some stress levels using molecular dynamics (MD) simulation. The polycrystalline model in the base metal region under the different retaining stresses (305 MPa, 427 MPa and 549 MPa), the different stress rates (25 MPa/ps, 50 MPa/ps and 100 MPa/ps) and the cyclic loading history are applied and analyzed using MD simulation. The effects of retaining stress, stress rate and cyclic loading history on the creep deformation of the X80 pipeline steel are investigated. The primary creep increases with the increment of retain stress, but little moving dislocation is produced under 50% minimum yield stress (305 MPa), the primary creep at reloaded retain stress is lower than that of the first load, which is thought as the decrease of moving dislocations. The high stress-loaded rate also results in a decrease primary creep. In addition, the defects and dislocation density under different conditions are analyzed and the room temperature creep mechanism of the model is discussed. The results obtained from this study will provide a reference to the research of room temperature creep of X80 pipeline steel.

关键词： Ovarian cancer   Adjuvant chemotherapy   Propensity score   Taxane   Carboplatin   CANCER   IMPACT   TRIALS   WOMEN  

摘要： Background Previous studies on adjuvant chemotherapy for patients with ovarian clear cell carcinoma (OCCC) have included a limited number of Asian patients with surgical stage I OCCC, despite differences in OCCC survival by race and stage. The aim of this study was to estimate the survival effect of the number of cycles of adjuvant taxane plus carboplatin chemotherapy in Asian patients with surgical stage I OCCC. Methods We retrospectively identified 227 patients with surgical stage I OCCC at 14 institutions from 1995 to 2017. Kaplan-Meier analysis and Cox proportional hazard regression with inverse probability of treatment weighting (IPTW) adjustment were performed to evaluate overall survival (OS) and recurrence-free survival (RFS) in patients receiving <= 3 and 4-6 cycles of taxane plus platinum adjuvant chemotherapy. Results Eighty-nine and 138 patients received <= 3 and 4-6 cycles of adjuvant chemotherapy, respectively. There was no between-group difference in OS or RFS with or without IPTW adjustment. In Cox proportional hazards analysis, 4-6 cycles of adjuvant chemotherapy were not associated with improved OS (HR 1.090; 95% CI 0.518-2.291; p = 0.821) or RFS (HR 1.144; 95% CI 0.619-2.114; p = 0.669) compared to <= 3 cycles, even with IPTW adjustment. Subgroup analysis in different substages of stage I OCCC showed that the number of cycles of adjuvant chemotherapy had no impact on OS or RFS. Conclusion Three or fewer cycles of taxane plus carboplatin chemotherapy may be a reasonable treatment regime for patients with surgical staging I OCCC.

关键词： Primary cutaneous diffuse large B-cell lymphoma   Leg type   Primary cutaneous follicle center lymphoma   Cell-of-origin   Hans algorithm   Lymph2Cx algorithm   WHO-EORTC CLASSIFICATION   PARAFFIN-EMBEDDED TISSUE   MYD88 SOMATIC MUTATION   GENE-EXPRESSION   DISTINCT TYPES   LEG TYPE   PATHOGENESIS  

摘要： Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-celllike (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

关键词： Squamous cell carcinoma   Skin cancer   Lymph node metastasis   Prognosis   Parotid   RISK-FACTORS   SURVIVAL   SKIN   RECURRENCE   BURDEN  

摘要： Purpose To identify potential risk factors impacting on overall survival (OS) of patients affected by lymph node metastasis from cutaneous squamous cell carcinoma (cSCC) of the head and neck (HN), with special emphasis on primary tumor characteristics and pattern of nodal recurrence (intraparotid and/or cervical). Methods A bi-institutional retrospective study on consecutive patients affected by cervical and/or intraparotid NM from HN cSCC and surgically treated with curative intent from May 2010 to January 2020 was conducted. OS was considered the outcome of interest. Results The study included 89 patients (M:F = 3.4:1; median age, 78 years; range, 22-99). Among the primary tumor characteristics, the most relevant prognostic factors were diameter >= 4 cm (hazard ratio [HR] = 2.56, p = 0.010) and depth of infiltration >= 6 mm (HR = 3.54, p = 0.027). Cervical NM was associated with worse OS (HR = 2.09, p = 0.016) compared to purely intraparotid NM (5-year OS: 60.9% vs. 28.1%, p = 0.014). At multivariable analysis, age, immunosuppression, pT3-T4 categories and a high burden of nodal disease (> 2 NM) confirmed to be independent risk factors, whereas adjuvant radiotherapy was independently associated with better outcome. Conclusion This study confirms the association of several independent prognosticators related to the patient, primary tumor, and nodal burden status. Patients with cervical NM should be considered at risk for harboring a higher number of metastatic lymph nodes.

关键词： SARS-CoV-2   SARS-CoV-2 vaccination   primary immu-nodeficiency   ACE2 blocking antibody   SARS-CoV-2 spike protein antibody   antibody deficiency   common variable immunodeficiency   Good syndrome   mAb   SARS-CoV-2 IFN-gamma release assay   SARS-COV-2  

摘要： Background: Data on the safety and efficacy of coronavirus disease 2019 (COVID-19) vaccination in people with a range of primary immunodeficiencies (PIDs) are lacking because these patients were excluded from COVID-19 vaccine trials. This information may help in clinical management of this vulnerable patient group. Objective: We assessed humoral and T-cell immune responses after 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with PID and functional B-cell defects. Methods: A double-center retrospective review was performed of patients with PID who completed COVID-19 mRNA vaccination and who had humoral responses assessed through SARS-CoV-2 spike protein receptor binding domain (RBD) IgG antibody levels with reflex assessment of the antibody to block RBD binding to angiotensin-converting enzyme 2 (ACE2; hereafter referred to as ACE2 receptor blocking activity, as a surrogate test for neutralization) and T-cell response evaluated by an IFN-gamma release assay. Immunization reactogenicity was also reviewed. Results: A total of 33 patients with humoral defect were evaluated; 69.6% received BNT162b2 vaccine (Pfizer-BioNTech) and 30.3% received mRNA-1273 (Moderna). The mRNA vaccines were generally well tolerated without severe reactions. The IFN-gamma release assay result was positive in 24 (77.4%) of 31 patients. Sixteen of 33 subjects had detectable RBD-specific IgG responses, but only 2 of these 16 subjects had an ACE2 receptor blocking activity level of >= 50%. Conclusion: Vaccination of this cohort of patients with PID with COVID-19 mRNAvaccines was safe, and cellular immunity was stimulated in most subjects. However, antibody responses to the spike protein RBD were less consistent, and, when detected, were not effective at ACE2 blocking.

关键词： IFN-GAMMA   STEM-CELLS   T-CELLS   IN-VIVO   APOPTOSIS  

摘要： Pressure ulcer (PU) is a chronic wound often seen in patients with spinal cord injury and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. In this study, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II-expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFN-gamma in PU-derived wound fluid could induce major histocompatibility complex II expression in keratinocytes and that these wound fluid-treated keratinocytes inhibited autologous T-cell activation. In line with this observation, we found that T cells from PUs enriched with major histocompatibility complex II+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared with that of acute wounds and intact skin, providing insights into PU pathology and the future development of tailored wound therapy.