Ultrastructural identification of cholinergic neurons in the external cuneate nucleus of the gerbil: acetylcholinesterase histochemistry and choline acetyltransferase immunocytochemistry

Summary Using acetylcholinesterase histochemical and choline acetyltransferase immunocytochemical localization methods, this study has provided conclusive evidence for the existence of cholinergic neurons in the external cuneate nucleus of gerbils. By light microscopy, both acetylcholinesterase and choline acetyltransferase labelling was confined to the rostral portion of the external cuneate nucleus. Ultrastructurally, acetylcholinesterase reaction products were found in the nuclear envelope, cisternae of rough endoplasmic reticulum and Golgi saccules of some somata and large dendrites as well as in the membranes of small dendrites, myelinated axons and axon terminals. These neuronal elements were also stained for choline acetyltransferase; immunoreactivity was associated with nuclear pores, nuclear envelope, perikaryal membrane and all the membranous structures within the cytoplasm. Of the total choline acetyltransferase-labelled neuronal profiles analysed, 79% were myelinated axons, 15% dendrites, 4% somata and 2% axon terminals. The immunostained axon terminals consisted of two types containing either round (Rd type; 62.5%) or pleomorphic (Pd type; 37.5%) vesicles. Both were associated directly with choline acetyltransferase-positive dendrites. In contrast to the paucity of choline acetyltransferase-labelled axon terminals, numerous choline acetyltransferase-positive myelinated axons were present. It may thus be hypothesized that most, if not all, of the external cuneate nucleus cholinergic neurons are projection cells; such cells may give rise to axonal collaterals which synapse onto their own dendrites for possible feedback control. Choline acetyltransferase-positive dendrites were contacted by numerous unlabelled presynaptic boutons, 60% of which contained round or spherical synaptic vesicles (Rd boutons) and 40% flattened vesicles (Fd boutons), suggesting that these neurons are under strong inhibitory control. The preferential concentration of cholinergic components in the rostral external cuneate nucleus may be significant in the light of the highly organized somatotopy in the external cuneate nucleus and its extensive efferent projections to medullary autonomic-related nuclei. Our results suggest that the cholinergic neurons may be involved in somatoautonomic integration.     

人乳腺病变组织AgNORs的形态定量分析

目的：探讨计算机图像分析技术对乳腺肿瘤核仁组成区相关嗜银蛋白（AgNORs）表达在病理学诊断中的意义。方法：选取乳癌、乳腺结构不良、乳腺纤维腺瘤及正常乳腺组织各20例，应用图像分析系统和嗜银染色技术，对乳腺病变组织的AgNORs进行形态计量学分析，观察每个细胞的胞核面积、核周长以及AgNOR颗粒数目、颗粒面积、AgNOR的大颗粒数、形态因子、面积比值、平均面积等8项参数。结果：正常乳腺及乳腺结构不良、乳腺纤维腺瘤组织的细胞核面积、核周长以及AgNOR颗粒数目、颗粒面积明显小于乳癌组织（P＜0．01），AgNOR的大颗粒数、形态因子、面积比值、平均面积在乳癌组织与乳腺纤维腺瘤及正常乳腺组织间差异有统计学意义（P＜0．05）。上述8项参数4组间多类判别分析回代符合率为72．5％，癌和非癌的判别回代符合率达100％。结论：图像分析对于乳腺良、恶性病变的鉴别诊断具有重要价值，是一精确、客观的AgNOR定量研究手段。     

Gender-specific response to isoflurane preconditioning in focal cerebral ischemia.

Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1(+/+) and Akt1(-/-) mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.     

Frailty评分对枸橼酸伊沙佐米治疗多发性骨髓瘤不良反应的预测价值

目的 探讨Frailty评分对枸橼酸伊沙佐米治疗多发性骨髓瘤(multiple myeloma, MM)不良反应的预测价值。方法 选取MM患者72例,均予以枸橼酸伊沙佐米联合沙利度胺、地塞米松方案治疗,观察治疗效果及不良反应。并根据患者不良反应程度分为Ⅰ～Ⅱ级组和Ⅲ～Ⅳ级组。比较2组Frailty评分;采用Cox回归模型分析化疗相关Ⅲ～Ⅳ级不良反应的影响因素;采用ROC曲线模型分析Frailty评分对化疗相关Ⅲ～Ⅳ级不良反应的预测价值。结果 72例MM患者均实施枸橼酸伊沙佐米治疗,总有效率为80.55%;出现不良反应70例、以乏力占比最高,发生率为72.22%,其次为淋巴细胞降低25.00%、贫血18.06%,未出现任何不良反应2例。Ⅲ～Ⅳ级组Frailty评分高于Ⅰ～Ⅱ级组(P<0.05)。70例出现不良反应患者均随访12个月,其平均生存时间(22.30±2.28)个月。Cox回归分析结果显示,Frailty评分≥2分是MM患者发生Ⅲ～Ⅳ级不良反应的影响因素。ROC曲线分析显示,Frailty评分预测化疗相关Ⅲ～Ⅳ级不良反应AUC值为0.925(95%CI:0.816～1.00...     

中性粒细胞与淋巴细胞比值预测高龄卒中预后的价值

探讨中性粒细胞与淋巴细胞比值（NLR）对≥80岁急性缺血性脑卒中患者90 d预后的价值。方法 纳入2019年1月—2021年6月发病7 d内、≥80岁的缺血性卒中患者476例的相关信息、影像结果、随访结果,按照入组患者NLR的四分位数间距分为Q1组（NLR ＜2.97）、Q2组（ 2.97≤NLR ＜4.49）、Q3组（ 4.49≤NLR ＜7.94）、Q4组 （NLR≥7.94）,每组119例。根据不良结局发生率绘制K-M曲线,比较各组在不同时期的生存概率。采用Cox多因素回归分析影响患者不良预后的因素。结果log-rank检验显示,四组患者的生存率存在差异,Q4组的90 d生存率显著低于Q1组(P＜0.05)。多因素Cox回归分析显示,校正危险因素后,高NLR和高NIHSS评分是90 d死亡率的独立危险因素(P＜0.05)。根据ROC曲线,高NLR预测患者90 d死亡曲线下面积为0.74。结论 高NLR为影响≥80岁高龄急性缺血性卒中患者90 d预后的独立危险因素,对高龄急性缺血性脑卒中患者的90 d预后有预测价值     

腰椎间盘突出症与腰椎间盘突出症合并阻塞性睡眠呼吸暂停患者的对比研究

目的 探究腰椎间盘突出症（LDH）与阻塞性睡眠呼吸暂停（OSA）之间的关联,为LDH的临床诊治策略及治疗方案提供参考依据。方法 选取2018年1月—2020年3月中国医科大学附属第一医院骨科行外科手术治疗的485例LDH患者,按是否合并OSA进行分组研究。结果 485例LDH患者中合并OSA的307例,发生率为63.3%。LDH合并OSA组主观症状、临床症状、日常活动受限程度日本骨科协会（JOA）腰痛评分低于单纯LDH组（P <0.05）;两组膀胱功能JOA评分比较,差异无统计学意义（P> 0.05）;LDH合并OSA组视觉模拟评分法（VAS）评分高于单纯LDH组（P <0.05）。Pfirrmann 5级评分法中4、5级例数构成比LDH合并OSA组较单纯LDH组高（P <0.05）。两组患者的硬膜撕裂率、神经受损率、血肿率、切口感染率等并发症发生率比较,差异无统计学意义（P>0.05）。单纯LDH组与LDH合并OSA组术后3、6、12和24个月静息状态下JOA和VAS评分比较,采用重复测量设计的方差分析,结果：(1)不同时间点的JOA和VAS评分有差异（...     

Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens.     

NF1 mutations in neurofibromatosis 1 patients with plexiform neurofibromas

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder caused by genetic alterations of the NF1 gene on 17q11.2. About 30% of NF1 patients develop plexiform neurofibromas (PNFs), which often cause severe clinical deficits. To determine whether there is a certain genotype underlying PNFs or subtypes of PNFs, we screened 42 NF1 patients from 41 families with PNFs for mutations in the NF1 gene. In 33 out of the 41 (80%) unrelated patients NF1 mutations were found, 24 are novel while the other 9 have been described in previous studies. The 33 mutations included 23 nonsense and frameshift, six splice and four missense mutations. The tumors in these patients had various sizes and features/growth characteristics. No correlation was found between the type or location of the NF1 mutations and size, location or feature of the PNFs, suggesting that many types of NF1 mutations can lead to development of PNFs.     

Computerized analysis of mammographic parenchymal patterns for assessing breast cancer risk: effect of ROI size and location

The long-term goal of our research is to develop computerized radiographic markers for assessing breast density and parenchymal patterns that may be used together with clinical measures for determining the risk of breast cancer and assessing the response to preventive treatment. In our earlier studies, we found that women at high risk tended to have dense breasts with mammographic patterns that were coarse and low in contrast. With our method, computerized texture analysis is performed on a region of interest (ROI) within the mammographic image. In our current study, we investigate the effect of ROI size and ROI location on the computerized texture features obtained from 90 subjects (30 BRCA1/BRCA2 gene-mutation carriers and 60 age-matched women deemed to be at low risk for breast cancer). Mammograms were digitized at 0.1 mm pixel size and various ROI sizes were extracted from different breast regions in the craniocaudal (CC) view. Seventeen features, which characterize the density and texture of the parenchymal patterns, were extracted from the ROIs on these digitized mammograms. Stepwise feature selection and linear discriminant analysis were applied to identify features that differentiate between the low-risk women and the BRCA1/BRCA2 gene-mutation carriers. ROC analysis was used to assess the performance of the features in the task of distinguishing between these two groups. Our results show that there was a statistically significant decrease in the performance of the computerized texture features, as the ROI location was varied from the central region behind the nipple. However, we failed to show a statistically significant decrease in the performance of the computerized texture features with decreasing ROI size for the range studied.