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关键词： CYP1A   Flatfish   histopathology   organophosphates   type B esterases  

摘要： The toxicity of malathion to Solea senegalensis was studied in a static renewal bioassay during its first month of larval life (between 4 and 30 dph). Through the use of different biomarkers and biochemical, cellular and molecular approaches (inhibition of cholinesterases [ChEs], changes in cytochrome P450-1A [CYP1A] and the study of histopathological alterations), the effects of three concentrations of malathion (1.56, 3.12, and 6.25 mu g/L) have been analyzed. In subacute exposure, malathion inhibited cholinesterase activities (AChE, BChE, CbE) in a dose- and time-dependent manner, ranging the inhibition percentage from 20% to 90%. However, the expression levels of CYP1A and AChE transcripts or proteins were not modified. Additionally, exposure to malathion provoked histopathological alterations in several organ systems of Senegalese sole in a time- and dose dependent way, namely disruption of parenchymal architecture in the liver, epithelial desquamation, pyknotic nuclei and steatosis in the intestine, disorganization of supporting cartilage, and sings of hyperplasia and hypertrophy in the gills and degeneration of the epithelial cells from the renal tubules. Malathion exposure also provoked strong disorganization of cardiac fibers from the heart. The findings provide evidence that exposure to sublethal concentrations of malathion that provoked serious injury to the fish S. senegalensis, were below the expected environmental concentrations reported in many other ecosystems and different fish species,revealing a higher sensitivity for Solea senegalensis to malathion exposure, thus reinforcing its use as sentinel species for environmental pollution in coastal and estuarine environments.

关键词： castration   CD34   hormonal metabolism   paracrine signaling   reactive stroma   senescence   smooth muscle cells   stem cells   telocytes   tissue organization  

摘要： Advances in prostatic stroma studies over the past few decades have demonstrated that the stroma not only supports and nourishes the gland's secretory epithelium but also participates in key aspects of morphogenesis, in the prostate's hormonal metabolism, and in the functionality of the secretory epithelium. Furthermore, the stroma is implicated in the onset and progression of prostate cancer through the formation of the so-called reactive stroma, which corresponds to a tumorigenesis-permissive microenvironment. Prostatic stromal cells are interconnected and exchange paracrine signals among themselves in a gland that is highly sensitive to endocrine hormones. There is a growing body of evidence that telocytes, recently detected interstitial cells that are also present in the prostate, are involved in stromal organization, so that their processes form a network of interconnections with both the epithelium and the other stromal cells. The present review provides an update on the different types of prostate stromal cells, their interrelationships and implications for prostate development, physiology and pathological conditions.

关键词： Sulfur dioxide   Diabetes mellitus   Glycemic indices   Blood glucose   insulin   HbA1c   Pancreatic tissue   Beta cells  

摘要： Sulfur dioxide (SO2) is a ubiquitous air pollutant. Recent studies suggest that SO2 is a momentous risk factor for diabetes mellitus (DM). The present investigation aimed to evaluate the effects of SO2 exposure on histopathology and morphometry of pancreatic islet cells and serum glycemic indices in rats. Sixteen male Wistar rats were divided equally into SO2 and control groups. SO2 group was exposed to 10 parts per million (ppm) SO2 for 5 weeks (6 days a week, 3 h/day) and control group to filtered air for the same time as SO2 group. Blood serums were collected and pancreatic tissue isolated. Glycemic indices were measured. Pathological and morphometric changes were studied in the pancreatic tissues. Exposure to SO2 caused a significant increase in blood glucose but did not significantly change insulin and HbA1c serum levels and HOMA-IR. There were significant differences in vascular congestion (p= 0.02) and insulitis (p= 0.04) between the groups. SO2 inhalation significantly reduced beta cell number and beta-alpha cell ratio compared with the control group (p=0.03 and p<0.0001, respectively). These findings suggest that SO2 exposure damages pancreatic tissue which subsequently influences either the incidence of DM or the trend of diabetic complications.

摘要： The contributions that the R-Ras subfamily [R-Ras, R-Ras2/teratocarcinoma 21 (TC21), and M-Ras] of small GTP-binding proteins make to normal and aberrant cellular functions have historically been poorly understood. However, this has begun to change with the realization that all three R-Ras subfamily members are occasionally mutated in Noonan syndrome (NS), a RASopathy characterized by the development of hematopoietic neoplasms and abnormalities affecting the immune, cardiovascular, and nervous systems. Consistent with the abnormalities seen in NS, a host of new studies have implicated R-Ras proteins in physiological and pathologic changes in cellular morphology, adhesion, and migration in the cardiovascular, immune, and nervous systems. These changes include regulating the migration and homing of mature and immature immune cells, vascular stabilization, clotting, and axonal and dendritic outgrowth during nervous system development. Dysregulated R-Ras signaling has also been linked to the pathogenesis of cardiovascular disease, intellectual disabilities, and human cancers. This review discusses the structure and regulation of R-Ras proteins and our current understanding of the signaling pathways that they regulate. It explores the phenotype of NS patients and their implications for the R-Ras subfamily functions. Next, it covers recent discoveries regarding physiological and pathologic R-Ras functions in key organ systems. Finally, it discusses how R-Ras signaling is dysregulated in cancers and mechanisms by which this may promote neoplasia.

关键词： cholecystectomy   cholecystitis   cholecystolithiasis   cholecystostomy   pathological processes  

摘要： Background The incidence of biliary events (BE) following percutaneous cholecystostomy (PC) in acute cholecystitis (AC) patients is high. Therefore, definitive laparoscopic cholecystectomy (LC) is recommended. We aimed to investigate the optimal timing of LC following PC with regard to the clinical course and pathological findings. Methods All 744 AC patients with PC were included. The incidence and median number of BE were investigated with the concept of competing risks. The 344 patients with interval LC were divided into two groups based on the pathological findings of resected gallbladders: the acute/acute-and-chronic group (AANC group) (n = 221) and the chronic group (n = 123). A comparative analysis of the demographic data and perioperative outcomes was performed. Results Among the 744 AC patients with PC, 142 patients experienced recurrent BE. The cumulative incidence of BE was 26.6%, and the median time to recurrence was 67.5 days. The PC-to-LC days of the chronic group were longer than those of the AANC group (73.51 vs 63.00, P < .001). The multivariate analysis indicated that the operation time was longer in the AANC group than in the chronic group (P = .040). Conclusion In terms of the clinical course and sequential pathological changes in the gallbladder, a 9- to 10-week interval after PC is the optimal timing for LC.

关键词： F-18 FDG   PET   CT   MRI   Pathologic response   LARC   NAT  

摘要： Objective The purpose of the current study was to compare the diagnostic accuracies of F-18 FDG PET/CT and MRI for prediction of pathologic responses to neoadjuvant treatment (NAT) in locally advanced rectal cancer (LARC) patients based on a systematic review and meta-analyses. Methods The PubMed, Cochrane, and Embase databases were searched to identify studies that conducted direct comparisons of the diagnostic performance of F-18 FDG PET/CT and MRI for the prediction of pathologic response to NAT in patients with LARC from the earliest available date of indexing up to July 31, 2020. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR + and LR -), and we constructed summary receiver operating characteristic curves. Results In nine studies (427 patients), the pooled sensitivity of F-18 FDG PET/CT was 0.79 (95% CI 0.71-0.86) and the pooled specificity was 0.74 (95% CI 0.60-0.84). LR syntheses yielded an overall LR + of 3.1 (95% CI 1.9-5.0) and an LR - of 0.28 (95% CI 0.18-0.43). The pooled diagnostic odds ratio (DOR) was 11 (95% CI 5-26). The pooled sensitivity of MRI was 0.89 (95% CI 0.77-0.95) and the pooled specificity was 0.66 (95% CI 0.55-0.76). LR syntheses yielded an overall LR + of 2.6 (95% CI 1.9-3.6) and an LR - of 0.17 (95% CI 0.08-0.37). The pooled DOR was 15 (95% CI 6-42). In meta-regression analysis, no variable was identified as the source of the study heterogeneity. Conclusion F-18 FDG PET/CT and MRI showed similar diagnostic performances for the prediction of pathologic responses to NAT in patients with LARC. However, each modality can be a complement to other rather than being used singly.

摘要： Intraductal cribritorm (IDC) and invasive cribritorm morphologies are associated with worse prostate cancer outcomes. Limited retrospective studies have associated IDC and cribriform morphology with germline mutations in DNA repair genes, particularly BRCA2. These findings, which prompted the National Comprehensive Cancer Network (NCCN) Guidelines for Prostate Cancer and Genetic/Familial High- Risk Assessment to consider germline testing for individuals with IDC/cribriform histology, have been questioned in a recent prospective study. A deepened understanding of the molecular mechanisms driving disease aggressiveness in cribriform morphology is critical to provide more clarity in clinical decision making. This review summarizes the current understanding of IDC and cribriform prostate cancer, with an emphasis on clinical outcomes and molecular alterations. (C) 2021 Elsevier Inc.

关键词： Oryctolagus cuniculus   Animal paleopathology   Zooarchaeology   Taphonomy   Skeletal disorders  

摘要： Objective: To provide prevalence data for future comparative analysis of the health status of rabbits (Oryctolagus cuniculus) accumulated in the archaeological record. Materials: Two contrasting assemblages were analysed for pathological and sub-pathological changes: 1) an assemblage of domestic modern rabbit bones;and 2) a non-anthropogenic accumulation of archaeological rabbit remains. Methods: The lesions observed macroscopically, under magnification, and radiographically in both assemblages are quantified and described. Results: In the first assemblage, pathological and sub-pathological changes mostly affected the lower limb bones and primarily took two forms: diaphyseal periosteal proliferation and hypervascularised distal physes. Differential diagnosis of the periosteal proliferation suggests that pododermatitis is the most probable cause. In the second assemblage fractures were the most common lesions, but isolated examples of hypervascularised physes, periosteal proliferation, and musculo-skeletal stress markers were also identified. The pathological changes recorded is typical of a naturally-accumulated population of wild rabbits. Conclusions: The prevalence of pathological and sub-pathological skeletal changes in the rabbits, and thus their health status, are closely related to living conditions. This study demonstrates the value of systematically recording pathologies in rabbit bones. Significance: We contribute new data to help understand rabbit interactions with humans in the past and also the environment they inhabited. Limitations: Working with modern samples frequently means only incomplete skeletons are available for study. In these cases lesion prevalence always needs to be interpreted with caution. Suggestions for further research: Paleopathological studies of rabbit remains are remarkable for their absence. Further exhaustive research in this area is advised.

关键词： Neuroendocrine tumor   PET   CT   68Ga-DOTATATE   Ki-67   SUV   Mitotic index  

摘要： Objective 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing and staging neuroendocrine neoplasms (NEN). Unlike other PET tracers like FDG, the meaningfulness and use of standardized uptake values (SUVs) of 68Ga-DOTATATE is not well-established. This study aimed to determine if a correlation exists between intensity of 68Ga-DOTATATE uptake and markers of cellular proliferation. Methods This retrospective study included 79 patients with positive 68Ga-DOTATATE PET/CT and Ki-67 and/or mitotic index (MI) available on pathology report. SUVmax of the most intense lesion and the most intense organ-matched lesion were determined. Demographics and pathology results for Ki-67 and MI were collected from the electronic medical record. Correlations and trends for correlations of SUVmax to Ki-67 and MI were performed using Kruskal-Wallis and Cuzick trend tests. Results A trend for an association between SUVmax and Ki-67 grade was found;median SUVmax of Ki-67 < 3%, 3-20%, and > 20% was 35.2, 31.8, and 12.8 (p = 0.077), respectively. There was also a trend between SUVmax and Ki-67 categories in organ-matched lesions (p = 0.08). The median organ-matched SUVmax of MI < 2, 2-20, and > 20 lesions was 34.2, 18, and 21.7, respectively, (Cuzick trend test p = 0.066). The median SUVmax for small bowel, pancreatic, and other primary locations was 27.6, 46.9, and 9.3 (p < 0.01), respectively. Conclusions The association between 68Ga-DOTATATE SUVmax, histologic grade, and primary site of NEN demonstrates its potential use for prognostication, or potentially as a surrogate for histologic grading when biopsy is not possible.

关键词： Colletotrichum fructicola   Camellia oleifera   Anthracnose   Histopathological   Ultrastructure  

摘要： To clarify the histopathological characteristics of Camellia oleifera that were infected by Colletotrichum fructicola, this study utilized frozen tissue sections, whole-stain clearing and transmission electron microscopy to observe the time of transformation from biotrophic to necrotrophic when Co. fructicola infects leaves, as well as the colonization and expansion of the pathogenic fungus at different stages on the leaves. The Co. fructicola conidia produced germ tubes 2 h post-inoculation, and appressoria began to form 4 h after inoculation. There were two ways that pathogens can use to invade the leaves of Ca. oleifera. One was to directly penetrate the host cuticle, while the other involved invasion from the stomata of the host using germ tubes or hyphae. A few infection vesicles could then be observed in the leaf tissue, and the infection vesicles produce thicker septal primary hyphae after 24 h of infection. When the infection reached the 40 h point, the fungus started to produce secondary hyphae with smaller diameter than that of the primary hyphae and gradually expanded into the adjacent cells. Transmission electron microscopy revealed that when the secondary hyphae entered the mesophyll cells, the contents in the cells were digested and a cavity gradually formed, indicating that the cells had been killed. Thus, the appearance of the secondary hyphae marked the point at which Co. fructicola entered into a destructive necrotrophic stage.