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Context.--Bone marrow (BM) samples are obtained through aspiration and trephine biopsy. Hemophagocytic lymphohistiocytosis (HLH) has been largely studied in BM aspirate smears. Objective.--To investigate the histologic features of HLH in trephine biopsy. Design.--Patients with hemophagocytosis in BM aspirate smears were assigned to HLH (n = 127) and non-HLH (n = 203) groups. We quantified hematoxylin-eosin and CD68 immunohistochemical staining of their trephine biopsies. Results.--No significant correlation was noted in the hemophagocytosis count between aspirate smears and trephine biopsies. Compared with the non-HLH group, the HLH group had a higher hemophagocytosis count (13 versus 9 per tissue section, P = .046), lower percentage of the adipocytic area (36.7% versus 50.3%, P < .001), and higher percentage of the foamy area (19.1% versus 14.5%, P < .001). The HLH group had more histiocyte infiltrates (total histiocyte density, 9.2% versus 7.3%; P < .001) and more fat-infiltrating histiocytes (histiocyte density of the fat-associated part [HD-FA], 7.6% versus 6.2%; P < .001). We identified the following poor prognostic factors in the HLH group: age 50 years or older (median overall survival [mOS], 95 versus 499 days; P = .04), Epstein-Barr viruspositive T-cell lymphoproliferative diseases (EBV+TLPDs) (mOS, 51 versus 425 days; P < .001), hemophagocytosis count of 6 or higher per tissue section (mOS, 66 versus 435 days; P = .02), and HD-FA of 9% or greater (mOS, 61 versus 359 days; P = .02). Multivariate analysis revealed that age 50 years or older (hazard ratio [HR], 2.38; P < .001), EBV+TLPDs (HR, 2.07; P < .001), and hemophagocytosis count of 6 or higher per tissue section (HR, 2.07; P = .002) were independent prognostic factors for HLH. Conclusions.--The HLH group had higher hemophagocytic activity, higher cellularity, a more foamy appearance, more histiocyte infiltrates, and more fat-infiltrating histiocytes. High hemophagocytic activity and marked histiocyte infiltrates in the BM fat were associated with poorer prognosis. doi: 10.5858/arpa.2021-0381-OA, Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic inflammatory syndrome. (1-3) Primary HLH is a group of inherited diseases with impaired cytotoxicity of T or natural killer (NK) cells. (1-5) Secondary [...]

Objective To investigate the effect of astragaloside Ⅳ on the injury of SK⁃N⁃SH cell in Parkinson's disease (PD) induced by 1 ⁃ methy ⁃ 4 ⁃ phenylpyridine (MPP＋) and its mechanism. Methods Human neuroblastoma cell line SK ⁃N ⁃SH was cultured to logarithmic growth stage, which were randomized to routine culture (control group), MPP＋ induction (MPP＋ group), astragaloside Ⅳ 10 mg/ml + MPP＋ induction (astragaloside Ⅳ 10 mg/ml group), astragaloside Ⅳ 30 mg/ml + MPP＋ induction (astragaloside Ⅳ 30 mg/ml group), astragaloside Ⅳ 30 mg/ml + MPP＋ induction + Janus kinase 2 (JAK2) inhibitor AG490 (JAK2 inhibitor group). Cell survival was detected by methyl thiazolyl tetrazolium (MTT) assay, cell apoptosis was detected by flow cytometry, reactive oxygen species (ROS) level was detected by DCFH ⁃ DA fluorescence probe, lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activities were detected by enzyme method. And the relative expression levels of phosphorylated Janus kinase 2 (pJAK2) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) proteins in JAK2 ⁃ STAT3 signal transducer pathway were detected by Western blotting. Results There were significant differences in cell survival rate (P = 0.000), apoptosis rate (P = 0.000), ROS content (P = 0.000), LDH activity (P = 0.000), SOD activity (P = 0.003), pJAK2 (P = 0.000) and pSTAT3 (P = 0.000) proteins relative expression levels among different SK ⁃ N ⁃ SH groups. Further pairwise comparison showed that compared with the control group, the cell survival rate (P = 0.000, 0.001, 0.049, 0.000), SOD activity (P = 0.000, 0.002, 0.012, 0.000), relative expression levels of pJAK2 (P = 0.003, 0.006, 0.036, 0.002) and pSTAT3 (P = 0.001, 0.002, 0.024, 0.001) proteins were decreased in MPP＋ group, astragaloside Ⅳ 10 mg/ml and 30 mg/ml groups, JAK2 inhibitor group, but the cell apoptosis rate (P = 0.001, 0.001, 0.001, 0.000), ROS content (P = 0.000, 0.001, 0.002, 0.000) and LDH activity (P = 0.000, 0.002, 0.038, 0.000) were increased. Compared with MPP＋ group, the survival rate (P = 0.016, 0.000), SOD activity (P = 0.003, 0.001), relative expression of pJAK2 (P = 0.013, 0.002) and pSTAT3 (P = 0.018, 0.002) proteins increased in astragaloside Ⅳ 10 mg/ml and 30 mg/ml groups, which the apoptosis rate (P = 0.021, 0.008), ROS content (P = 0.031, 0.003) and LDH activity (P = 0.001, 0.000) decreased. Compared with astragaloside Ⅳ 10 mg/ml group, the cell survival rate (P = 0.002), SOD activity (P = 0.027), relative expression of pJAK2 (P = 0.007) and pSTAT3 (P = 0.006) proteins were increased in astragaloside Ⅳ 30 mg/ml group, but ROS content (P = 0.019) and LDH activity (P = 0.011) decreased, while apoptosis rate (P = 0.016), ROS content (P = 0.030) and LDH activity (P = 0.004) increased in JAK2 inhibitor group, and SOD activity (P = 0.004), the relative expression of pJAK2 (P = 0.001) and pSTAT3 (P = 0.005) proteins were decreased. Compared with astragaloside Ⅳ 30 mg/ml group, cell survival rate (P = 0.001), SOD activity (P = 0.001), the relative expression of pJAK2 (P = 0.000) and pSTAT3 (P = 0.001) proteins in JAK2 inhibitor group were decreased, but the apoptosis rate (P = 0.004), ROS content (P = 0.002) and LDH activity (P = 0.001) were increased. Conclusions Astragaloside Ⅳ can reduce MPP＋ induced SK ⁃ N ⁃ SH cell injury in PD, which may be related to the activation of JAK2 ⁃ STAT3 signal transducer pathway.

Aim: Within the intensively‐studied, well‐documented latitudinal diversity gradient, the deep‐sea biodiversity of the present‐day Norwegian Sea stands out with its notably low diversity, constituting a steep latitudinal diversity gradient in the North Atlantic. The reason behind this has long been a topic of debate and speculation. Most prominently, it is explained by the deep‐sea glacial disturbance hypothesis, which states that harsh environmental glacial conditions negatively impacted Norwegian Sea diversities, which have not yet fully recovered. Our aim is to empirically test this hypothesis. Specific research questions are: (1) Has deep‐sea biodiversity been lower during glacials than during interglacials? (2) Was there any faunal shift at the Mid‐Brunhes Event (MBE) when the mode of glacial–interglacial climatic change was altered? Location: Norwegian Sea, deep sea (1819–2800 m), coring sites MD992277, PS1243, and M23352. Time period: 620.7–1.4 ka (Middle Pleistocene–Late Holocene). Taxa studied: Ostracoda (Crustacea). Methods: We empirically test the deep‐sea glacial disturbance hypothesis by investigating whether diversity in glacial periods is consistently lower than diversity in interglacial periods. Additionally, we apply comparative analyses to determine a potential faunal shift at the MBE, a Pleistocene event describing a fundamental shift in global climate. Results: The deep Norwegian Sea diversity was not lower during glacial periods compared to interglacial periods. Holocene diversity was exceedingly lower than that of the last glacial period. Faunal composition changed substantially between pre‐ and post‐MBE. Main conclusions: These results reject the glacial disturbance hypothesis, since the low glacial diversity is the important precondition here. The present‐day‐style deep Norwegian Sea ecosystem was established by the MBE, more specifically by MBE‐induced changes in global climate, which has led to more dynamic post‐MBE conditions. In a broader context, this implies that the MBE has played an important role in the establishment of the modern polar deep‐sea ecosystem and biodiversity in general. [ABSTRACT FROM AUTHOR]