Diagnostic significance of the histopathology of bone marrow macrophages in forensic autopsies

Forensic pathologists often encounter autopsies that require an assessment of antemortem general conditions (e.g., infection, metabolic disorders). To establish evaluation clues for such cases, we quantitatively examined macrophages and the general pathology of bone marrow in samples from 180 forensic autopsy cases of decedents with various conditions. Hematoxylin-eosin staining, Berlin blue staining, and immunostainings for CD163, CD138, and CD61 were performed. We determined the numbers per field (density) of total macrophages, swollen macrophages, macrophages with hemophagocytosis, and hemosiderin-laden macrophages. Each density was standardized by identifying its ratio to the total number of macrophages. The decedents' background data (cause of death, other pathological findings, postmortem interval, antemortem symptoms, and presence of resuscitation) were extracted. No correlations were found between the postmortem interval and the other decedent data, indicating that these data are not affected by postmortem changes. In the group in which inflammatory disease was the cause of death, there were significant elevations in the ratio of the swollen macrophage density to total macrophages. Significantly higher ratios of the density of swollen and hemophagocytic macrophages were observed in the group in which conditions with a prolonged agonal period were the cause of death. The group with a return of spontaneous circulation to resuscitation showed a significantly higher ratio of macrophage density with hemophagocytosis. This study provides the first statistical analysis focused on bone marrow histopathology in forensic autopsies. The results will be useful for elucidating causes of death and agonal-period conditions.     

女性致密性骨炎血清骨转换生化标志物水平变化研究

背景 致密性骨炎（OCI）和其他疾病有时难以鉴别，探讨血清骨转换生化标志物可为OCI的鉴别诊断提供依据。 目的 探索女性OCI患者的血清骨转换生化标志物的水平变化及临床意义。 方法 回顾性选取2013年6月至2022年2月在北京积水潭医院门诊及住院诊断为OCI的61例女性患者作为观察组，年龄15~50岁，平均（33.8±6.6）岁，病程2周~15年。选择同期61例女性体检健康者作为对照组，年龄15~48岁，平均（35.6±7.6）岁。比较两组一般临床资料和血清骨转换生化标志物水平，并对血清骨转换生化标志物与病情相关指标进行相关性分析。 结果 观察组血清白蛋白（45.4±2.9）g/L低于对照组（46.5±2.8）g/L（t=2.190，P<0.05）。血清骨转换生化标志物比较结果显示，观察组血清1型胶原羧基末端肽β特殊序列（β-CTX）〔0.28（0.23，0.37）μg/L〕、N-端骨钙素（OC）〔13.1（11.2，16.2）μg/L〕、25-羟维生素D3〔25-（OH）VD3〕〔（14.1±5.1）μg/L〕低于对照组〔0.36（0.29，0.48）μg/L，15.6（13.7，17.3）μg/L，（17.5±6.6）μg/L〕（Z=-2.983、-3.255，t=3.081，P<0.05）。长病程亚组OC水平〔14.6（12.4，18.5）μg/L〕高于短病程亚组〔11.7（10.2，14.0）μg/L〕（Z=-2.407，P<0.05）。多孕亚组β-CTX〔0.25（0.22，0.32）μg/L〕、OC水平〔12.2（10.3，15.0）μg/L〕低于非多孕亚组〔0.33（0.26，0.44）μg/L、13.4（12.0，18.8）μg/L〕（Z=-2.486、-1.897，P<0.05）。相关性分析显示，观察组血清1型前胶原氨基端延长肽（tP1NP）与妊娠次数、生产次数均呈负相关（rs=-0.276、-0.298，P<0.05），OC与体质指数（BMI）、视觉模拟评分法（VAS）评分、妊娠次数均呈负相关（rs=-0.284、-0.374、-0.360，P<0.05），25-（OH）VD3水平与BMI呈正相关（rs=0.275，P<0.05）。 结论 女性OCI患者血清OC、β-CTX水平明显降低，可为鉴别其他疾病提供依据；血清OC水平可以反映OCI患者的严重程度，同时OC水平与患者妊娠次数相关；tP1NP与妊娠次数、生产次数相关。     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

DHS和PFNA固定治疗老年股骨粗隆间骨折的疗效

目的对比动力髋螺钉(dynamic hip screw,DHS)治疗和股骨近端抗旋髓内钉(proximal femoral nail anti-rotation,PFNA)固定治疗老年股骨粗隆间骨折疗效。方法纳入本院收治的45例采用PFNA固定治疗的老年股骨粗隆间骨折患者作为研究组,研究时间为2017年11月-2018年11月;回顾性分析2016年11月-2017年11月在我院采用DHS治疗的45例老年股骨粗隆间骨折患者的临床资料,作为对照组。记录两组的相关手术指标,观察手术并发症情况。结果研究组的手术时间和骨折愈合时间均短于对照组,术中出血量明显少于对照组,术后疼痛VAS评分均明显低于对照组(P<0.05)。对照组的并发症发生率高于研究组(P<0.05)。结论PFNA固定治疗比DHS治疗老年股骨粗隆间骨折更加安全有效,值得临床借鉴和应用。     

The appearance of breast cancer metastases on dry bone: Implications for forensic anthropology

Breast carcinoma is a major cause of morbidity and mortality in women. The study of bone pathologies presents considerable potential in anthropology, paleopathology, forensic science and medicine. In this paper, we present and discuss metastatic lesions found in the skeletons of known individuals from the CAL Milano Cemetery Skeletal Collection, clinically diagnosed with breast cancer during life. Fourteen skeletons from a contemporary and identified collection were macroscopically studied and metastases were identified by comparison with clinical literature. As a result, bone metastases were observed in 43% of the study sample. They were located most commonly on the ribs (28.1%), pelvic girdle (19.8%), vertebrae (15.6%), skull (15.6%), scapulae (10.2%) as well as proximal segment of the femora (8.4%) and humeri (2.4%) respectively, favoring sites of high vascularization. The majority of the lesions were osteolytic, although osteoblastic and mixed metastases did occur. Osteolytic metastases appear as coalescent porosity or round to oval perforating lesions on bones with denticulated margins and pitted surrounding bone, whereas osteoblastic metastases thickened the existing trabecula (spongiosclerosis). Mixed metastases were perforating lytic lesions exposing the osteoblastic activity in the underlying trabecular bone. These results, consistent with the data from the literature, strengthen the diagnostic criteria for metastases and illustrate the aspect of bone metastases in breast carcinoma.     

动物瘢痕模型的相关研究进展

皮肤损伤后的异常愈合会导致病理性瘢痕的产生。病理性瘢痕的出现不仅影响美观,严重时还会造成心理和生理功能障碍。病理性瘢痕的机制研究对于瘢痕治疗有极为重要的意义。其中,动物瘢痕模型是目前研究病理性瘢痕的重要模型手段之一。理想的动物瘢痕模型应该在组织学、细胞学等层面尽可能接近于人类的病理性瘢痕。该文分别从传统技术动物瘢痕中的啮齿类动物模型、兔耳模型和猪模型,以及新技术动物瘢痕模型这两个方面,结合近年来在瘢痕领域应用较多的研究,进行了相应系统的阐述。     

卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能和骨密度的影响分析

目的探究卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能、骨密度的影响。方法92例成人癫痫患者作为研究对象,随机分为左乙拉西坦组与卡马西平组,各46例。左乙拉西坦组采用左乙拉西坦治疗,卡马西平组采用卡马西平治疗。比较两组患者治疗前及治疗6个月后认知功能[语言智商(VIQ)、操作智商(PIQ)、总智商(FIQ)]评分、骨密度(腰椎、股骨大转子、股骨颈)变化情况。结果治疗6个月后,两组患者VIQ、PIQ、FIQ评分均较治疗前显著提升,且左乙拉西坦组患者VIQ评分(101.2±3.1)分、PIQ评分(108.1±2.3)分、FIQ评分(105.2±1.8)分均明显高于卡马西平组的(95.1±2.8)、(94.1±2.0)、(93.5±1.6)分,差异有统计学意义(P<0.05)。治疗6个月后,卡马西平组患者腰椎、股骨大转子、股骨颈骨密度均较治疗前显著下降,且明显低于卡马西平组,差异有统计学意义(P<0.05);左乙拉西坦组治疗6个月后腰椎、股骨大转子、股骨颈骨密度与治疗前比较差异无统计学意义(P>0.05)。结论左乙拉西坦与卡马西平治疗成人癫痫,左乙拉西坦更能明显提升患者认知功能,且对患者骨密度无影响。