Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age‐related change in function across cortical and subcortical sub‐regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross‐sectional adult age differences in estimates of D2‐like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [¹⁸F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6–16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3–5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0–2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.     

CK10和CK17在早期宫颈癌组织中的表达及其预测预后的价值

目的:CK10和CK17在早期宫颈癌组织中的表达及其预测预后价值的意义。方法:采用标准免疫组化SP法检测CK10和CK17在60例正常宫颈组织、60例宫颈上皮内瘤变和120例宫颈癌组织中的表达情况。结果:CK10的阳性表达定位于细胞质，在正常宫颈组织、CIN、宫颈癌患者中阳性表达率分别为80.00%、50.00%和21.67%，三组相比差异有显著统计学意义（P<0.001）。CK17的阳性表达定位于细胞质，三组阳性表达率分别为0%、46.67%和80.00%，三组相比差异显著（P<0.001）。χ2检验分析宫颈癌组织中CK17的表达与患者FIGO分期、是否有淋巴结转移、病理分型、组织分化无关（P>0.05）；CK10的表达与患者FIGO分期、是否有淋巴结转移、病理分型无关，与组织分化程度有关（P=0.021）。Kaplan-Meier生存分析显示:早期宫颈癌手术治疗患者的1年、3年、5年生存率分别为:100%、96.7%、93.3%；CK10 阴性组和阳性组5年生存率分别为91.5%和100%；CK17阴性组和阳性组5年生存率分别为100%和91.7%，差异均无统计学意义（P>0.05）。单因素分析显示CK10及CK17的表达和预后无关（P>0.05），年龄、是否淋巴结转移、FIGO分期、组织分化、病理分型均与预后相关（P<0.05）。根据CK17和CK10的表达情况将患者分为四组，CK17阳性CK10阴性组患者1年、3年、5年生存率分别为:100%、94.9%、89.7%，余CK17阳性CK10阳性组、CK17阴性CK10阳性组、CK17阴性CK10阴性组5年生存率分别为:100%、100%、100%，差异无统计学意义（P=0.211）。结论:CK10的表达水平与宫颈病变严重程度呈负相关，CK17的表达水平与宫颈病变严重程度呈正相关，两者可能参与了宫颈癌的发生发展，但CK17和CK10在预测宫颈癌患者预后方面的价值不大，而年龄、是否淋巴结转移、FIGO分期、组织分化、病理分型是影响患者预后的重要因素。     

甲状腺乳头状癌组织常染色体和性染色体STR基因座变异分析

目的：探讨甲状腺乳头状癌组织中短串联重复序列（STR）基因座变异规律以及显微切割技术在肿瘤组织鉴定中的应用，为甲状腺乳头状癌组织的个体识别及亲缘关系鉴定提供依据。方法：收集43例人甲状腺乳头状癌和癌旁正常组织经激光显微切割获取肿瘤细胞和间质细胞，采用Chelex-100法提取DNA，分别采用Goldeneye^® DNA 22NC、Goldeneye^® DNA 27YB和Goldeneye^® DNA 17X试剂盒进行常染色体和性染色体STR基因座PCR扩增，ABI 3500遗传分析仪检测进行STR分型。结果：甲状腺乳头状癌组织肿瘤间质细胞与对应癌旁组织的STR分型一致。43例癌组织的肿瘤细胞有9例STR基因座发生了变异，在常染色体和X染色体联合检测的37个STR基因座共检出11次变异（常染色体变异7次，X染色体变异4次），其中等位基因增加3次，部分杂合性丢失6次，出现新等位基因2次，并且同一甲状腺乳头状癌肿瘤细胞可同时发生多种变异。Y染色体STR基因座没有检出变异。结合实验结果与患者临床资料分析，STR基因座的变异与甲状腺乳头状癌患者的临床分期、性别无明显相关关系，与患者的年龄正相关，差异具有统计学意义（P < 0.05）。结论：甲状腺恶性肿瘤组织常染色体和X染色体STR基因座存在变异，而且变异更可能发生在年龄大的甲状腺乳头状癌组织中，在司法鉴定中进行STR分型时应谨慎判型。显微切割技术可准确分离间质细胞，是解决此类恶性肿瘤组织检材涉及的案件进行身源鉴定的有效手段。     

柴胡皂苷D通过抑制EMT和细胞干性抑制人结直肠癌细胞SW480的迁移和侵袭

目的:研究柴胡皂苷D（saikosaponin-D，SSD）对人结直肠癌细胞SW480迁移和侵袭能力的影响，并初步探讨SSD抑制细胞迁移和侵袭的机制。方法:MTT检测SSD对细胞增殖的影响。划痕实验和Transwell迁移实验研究SSD对细胞迁移能力的影响。Transwell侵袭实验研究SSD对细胞侵袭能力的影响。Western-blot检测SSD对上皮间质转化（epithelial mesenchymal transformation，EMT）相关蛋白（E-cadherin、N-cadherin和Vimentin）表达的影响。克隆球形成实验研究SSD对细胞干性的影响。结果:在划痕实验和Transwell迁移实验中，SSD显著抑制SW480的迁移能力（P<0.05）。在Transwell侵袭实验中，SSD显著抑制SW480的侵袭能力（P<0.05）。SSD处理后，细胞E-cadherin的表达增高，N-cadherin和Vimentin的表达降低（P<0.05），同时SSD抑制SW480细胞克隆球的形成（P<0.05）。结论:柴胡皂苷D通过抑制EMT和细胞干性抑制人结直肠癌细胞SW480的迁移和侵袭。     

基于物料性质表征技术的蒲地蓝消炎口服液 儿童用药顺应性改善研究

蒲地蓝消炎口服液安全有效,显效迅速,临床应用广泛,但在儿科用药领域,由于用药剂量不明确与口服顺应性差成为制约其发展的主要原因。基于此,本研究通过分析其问题产生的根源并深入探究其解决方案,通过物料性质表征技术、复合矫味技术、剂型优化技术以提升蒲地蓝消炎口服液的口服顺应性,同时探讨蒲地蓝消炎口服液的儿童精准用药策略,为儿童精准用药的临床前研究提供技术指导。     

柴胡皂苷D通过诱导自噬抑制人结直肠癌细胞SW480增殖的实验

目的:研究柴胡皂苷D（saikosaponin-D，SSD）对人结直肠癌细胞SW480自噬的影响，并探讨诱导的自噬对细胞增殖的影响。方法:Western-blot检测SSD对自噬相关蛋白LC3A/B和p62表达的影响，LC3翻转实验和GFP-RFP-LC3荧光实验验证自噬流的发生。Western-blot检测3-MA对SSD所诱导自噬的抑制作用，MTT和细胞计数实验研究3-MA抑制自噬后SSD对SW480细胞增殖的影响。结果:SSD能够诱导SW480细胞发生自噬，表现在LC3A/B II及LC3A/B II/I比值的增高、自噬经典底物蛋白p62的减少、LC3翻转试验阳性以及LC3荧光实验中黄色和红色荧光颗粒的增多（P＜0.05）。自噬抑制剂3-MA能够抑制SSD所诱导自噬的发生（P＜0.05），且3-MA抑制自噬后，SSD对SW480的增殖抑制效应减弱（P＜0.05），提示SSD诱导的自噬对细胞的增殖起抑制作用。结论:SSD通过诱导自噬抑制人结直肠癌细胞SW480的增殖。     

Recurrent BRCA1 Mutation,but no BRCA2 Mutation,in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Background: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. Methods: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. Results: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Conclusion: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.     

Percutaneous radiofrequency ablation versus open surgical resection for spinal osteoid osteoma

BACKGROUND CONTEXT

Both open surgical resection (OSR) and radiofrequency ablation (RFA) have been reported for spinal osteoid osteoma (OO).

Rates of reoperation and nonoperative intervention within 30 days of bariatric surgery

BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ² for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG.