Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons

The present study examined the effects of glutamate on the outgrowth of dendrites and axons in isolated hippocampal pyramidal-like neurons in cell culture. During the first day of culture the survival and outgrowth of these neurons was unaffected by high concentrations (up to 1 nM) of glutamate, quisqualic acid (QA), kainic acid (KA), and N-methyl-D-aspartic acid. Beginning on day 2 of culture high levels of glutamate, KA and QA were toxic to the majority of pyramidal neurons, while subtoxic levels of these agents caused a well-defined, dose-dependent, sequence of effects on dendritic outgrowth. At increasing concentrations of glutamate, QA, and KA, the following events were observed: (1) dendritic outgrowth rates were reduced, while axonal elongation rates were unaffected; (2) dendritic length was reduced, while axons continued to grow; (3) dendrites regressed dramatically, and axonal outgrowth rate was reduced. These dendrite-specific effects of glutamate were apparently mediated at the growth cones since focal application of glutamate to individual dendritic growth cones resulted in suppression of growth cone activity and a regression of the dendrite; axons were unaffected by focal glutamate application. Pharmacological tests using glutamate receptor agonists and antagonists demonstrated that receptors of the KA/QA type mediated the glutamate effects on outgrowth and survival. The calcium channel blocker Co2+ prevented both glutamate neurotoxicity and glutamate-induced dendritic regression. Ionophore A23187 and elevations in extracellular K+ levels each caused a dose-dependent series of outgrowth and survival responses similar to those caused by glutamate. Taken together, these results indicate that activation of glutamate receptors leads to the opening of voltage-dependent calcium channels; the resulting increases in calcium influx lead to the observed alterations in dendritic outgrowth and neuronal survival.     

Optical Pretargeting of Tumor with Fluorescent MORF Oligomers

Objective Pretargeting with radioactivity has significantly improved tumor to normal tissue radioactivity ratios over conventional antibody imaging in both animal studies and clinical trials. This laboratory is investigating DNA analogues such as phosphorodiamidate morpholinos (MORFs) for pretargeting using technetium-99m (^99mTc) for detection. However, the unique properties of fluorescence activation and quenching combined with oligomers with their unique properties of hybridization may be particularly useful when used together for pretargeting with optical detection. The use of linear fluorophore-conjugated oligomer duplexes have been little used in animals, and to our knowledge, have not previously been considered for pretargeting applications. Methods A MORF/cDNA pair was selected such that when hybridized, the fluorescence of the Cy5.5-conjugated 25 mer MORF (Cy5.5–MORF25) is inhibited with a BHQ3-conjugated 18 mer complementary DNA (BHQ3–cDNA18). The short BHQ3–cDNA18 was selected to dissociate in the presence of a long cMORF25 in the pretargeted tumor, thus releasing the inhibitor from the Cy5.5 emitter. In this manner, the Cy5.5 fluorescence will be inhibited everywhere but in the target. The dissociation was first examined in vitro by adding the duplex to the cMORF25 both in solution and immobilized on polystyrene microspheres and by surface plasmon resonance (SPR). Thereafter, biotinylated cMORF25 immobilized on streptavidin polystyrene microspheres were administered intramuscularly in one thigh of hairless SKH-1 mice as target while an identical weight of the identical microspheres but without the cMORF25 was administered in the contralateral thigh as control. The animals then received IV the Cy5.5–MORF25/BHQ3–cDNA18 duplex or equal molar dosage of single-chain Cy5.5–MORF25 and were imaged. Results The SPR studies showed that the immobilized cDNA18 rapidly captured the flowing MORF25 to provide a duplex with a slow dissociation rate constant. Furthermore, when cMORF25 was next allowed to flow over the now immobilized duplex, the cDNA18 was unable to prevent dissociation of the heteroduplex and the formation and release of the cMORF25-MORF25 homoduplex. Images of animals obtained soon after receiving the Cy5.5–MORF25 singlet showed intense whole body fluorescence obscuring the target thigh. However, only 5 minutes after receiving the Cy5.5–MORF25/BHQ3–cDNA18 duplex, the target thigh was clearly visible along with only the kidneys. Conclusions This first study of optical pretargeting provides a proof of concept that oligomer pretargeting found to be useful with radioactivity detection is applicable with fluorescent detection as well. In addition, our results demonstrate that by using linear oligomers for optical pretargeting, chain lengths (and base sequences) may be manipulated to provide duplexes with stabilities and fluorescence inhibition optimized for pretargeting and other in vivo applications of optical imaging.     

Increasing sampling density improves reproducibility of optical coherence tomography measurements.

PURPOSE: Published series of peripapillary retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) have sampled 100 evenly distributed points on a 360 degrees peripapillary circular scan. The goal of this study was to determine whether a four-fold increase in sampling density improves the reproducibility of OCT measurements. METHODS: Complete ophthalmic examinations, achromatic automated perimetry, and OCT imaging were performed in all patients. The OCT scanning consisted of three superior and inferior quadrantic scans (100 sampling points/quadrant) and three circular scans (25 points/quadrant). The RNFL thickness measurements and coefficient of variation (CV) were calculated for the superior and inferior quadrants for each sampling density technique. RESULTS: The study included 22 eyes of 22 patients (3 control subjects; 2 patients with ocular hypertension; and 17 patients with glaucoma). Quadrants with associated glaucomatous visual field loss on automated achromatic perimetry had thinner RNFLs than quadrants without functional defects for both the 25- and 100-points/quadrant scans. For quadrants associated with normal visual hemifields (n = 22), there was no difference between the 25- and 100-points/quadrant scans in mean RNFL thickness and CV. Among quadrants with visual field defects (n = 22), RNFL thickness measurements were thinner in the 25-points/quadrant scans than in the 100-points/quadrant scans. The CV for the 25-points/quadrant scans (25.9%) was significantly higher than that for the 100-points/quadrant scans (11.9%). CONCLUSION: Increasing the sampling density of OCT scans provides less variable representation of RNFL thickness. The optimal sampling density to achieve maximal reliability of OCT scans remains to be determined.     

LASIK术后角膜瓣再次复位的临床应用

目的:观察LASIK术后角膜瓣移位的原因及其再次复位的方法和效果。方法:对所有18眼LASIK术后角膜瓣移位的患者均进行再次复位。结果:所有LASIK术后角膜瓣的移位,再次复位后均获得了良好的视力及角膜瓣对位。结论:LASIK术后严密的观察、防止外伤、及时的处理是预防和治疗角膜瓣移位的有效方法。     

抑郁障碍患者主观与客观认知功能的差异性研究

背景 抑郁障碍患者的主观认知功能与客观认知功能存在差异。目前,关于主客观认知功能差异影响因素的研究有限。目的 探索抑郁障碍患者主观和客观认知功能的差异及其影响因素,为进一步理解抑郁障碍患者认知功能受损情况提供参考。方法 纳入2022年1月13日—2023年12月11日在成都市第四人民医院门诊就诊或住院治疗的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）抑郁障碍诊断标准的77例患者为研究对象。采用蒙哥马利-艾森贝格抑郁量表（MADRS）评定患者抑郁症状严重程度,采用抑郁感知缺陷问卷（PDQ-D）和中国简版神经认知成套测验（C-BCT）分别评定患者的主观认知功能和客观认知功能,采用席汉残疾量表（SDS）评定患者的社会功能,以临床总体印象量表-疾病严重程度量表（CGI-SI）评定患者病情严重程度。采用Pearson相关分析考查年龄、受教育年限、MADRS总评分、SDS总评分、CGI-SI评分与主客观认知功能及其差异的相关性。采用多元线性回归探索主客观认知功能差异的影响因素。结果 是否用药的抑郁障碍患者PDQ-D总评分和主客观认知功能差异（D值）比较差异均有统计学意义（t=-4.2...     

Isolated splenic metastasis of endometrial cancer 12 years after treatment: A case report and literature review

Rationale:The spleen is an uncommon metastatic organ for malignant solid tumors because of its special anatomy and microenvironment. Isolated splenic metastasis of endometrial cancer is an extremely rare clinical event, with only 17 cases reported in literature.Patient concerns:We report the case of a 58-year-old woman with abdominal distension and nausea for 7 months who had undergone surgery and chemotherapy for endometrioid adenocarcinoma 12 years previously. A space-occupying lesion in the upper pole of the spleen was observed on an abdominal ultrasound.Diagnosis:The spleen was resected, and splenic metastasis of endometrial adenocarcinoma was histologically confirmed.Interventions:Splenectomy was performed, and no lymph nodes or other metastases were observed. The patient received postoperative chemotherapy with 6 cycles of docetaxel and carboplatin.Outcomes:The patient recovered well 11 months postoperatively, with no evidence of recurrence or metastatic disease.Lesson:Since the time interval between the diagnosis of primary endometrial cancer and splenic metastasis may be very long, it may be necessary to monitor the recurrence of endometrial cancer after primary treatment.     

谢慧教授使用温针灸疗法治疗变应性鼻炎病例探析

目的 探究中医温针灸疗法对于变应性鼻炎的治疗原则。 方法 针刺百会、下关、合谷,并对足三里施以温针灸疗法治疗变应性鼻炎36例, 1次/周,3周为1个疗程,评价治疗效果。 结果 中医传统外治温针灸疗法治疗变应性鼻炎效果良好, 5例显效,27例明显好转,4例无明显改变,有效率达89%。 结论 使用温针灸以“健脾益气,升阳固卫”为原则,可有效改善变应性鼻炎鼻塞、流清涕、打喷嚏症状,为治疗变应性鼻炎提供一种有效的治疗方案。     

天冬泡腾颗粒剂处方配比优化研究

目的优化天冬泡腾颗粒剂的最佳处方配比。方法以pH值、粒度及溶化时限作为评价方法,采用正交试验设计,考察天冬提取浸膏、辅料用量对泡腾颗粒剂处方的影响。结果天冬泡腾颗粒剂最佳处方配比为天冬提取浸膏5.0 g、乳糖1.5 g、糊精3.0 g、淀粉4.0 g。结论该制剂处方稳定,可用于该制剂生产。     

合肥市社区居民健康状况及其影响因素分析

目的 了解社区居民健康状况及其影响因素,为合理配置社区卫生资源提供决策依据.方法 在合肥市39所CHS中心服务辖区内随机选择40户家庭,采用入户访谈调查全部家庭成员.结果 社区居民2 w患病率为80.0‰;年住院率为7.3%;慢性病患病率为16.4%;15岁及以上居民认为自身健康状况"好"、"一般"及"差"的比例分别为33.6%、58.5%、7.9%;医疗保障制度、文化程度、收入水平及生活行为是影响健康状况的重要因素.结论 在社区居民健康诊断的基础上,合理配置社区卫生资源,精心设计服务提供内容,不断满足社区居民卫生服务需求.     

An antibody against Siglec-15 promotes bone formation and fracture healing by increasing TRAP+mononuclear cells and PDGF-BB secretion

INTRODUCTION Siglec-15 is a member of the sialic acid-binding immunoglobulintype lectin (Siglecs) family, a group of cell-surface receptors that potentially reg...