Response rates in metastatic neuroendocrine tumors receiving peptide receptor radionuclide therapy and implications for future treatment strategies

BackgroundPeptide receptor radionuclide therapy is a targeted therapy used to treat unresectable somatostatin receptor-positive neuroendocrine tumors. The objective of this study was to evaluate response rates among neuroendocrine tumors of different primaries and identify factors relevant to future treatment strategies.MethodsWe retrospectively reviewed patients who received peptide receptor radionuclide therapy for neuroendocrine tumors from 2018 to 2019 at our institution. Patients were assessed with computed tomography/magnetic resonance imaging and ⁶⁸Ga-DOTATATE-positron emission tomography before and after 2 or 4 cycles of peptide receptor radionuclide therapy. Tumor response was evaluated by RECIST 1.1. Statistics included multinomial logistic regression models and Fisher exact test.ResultsTwenty-seven patients underwent 92 cycles of peptide receptor radionuclide therapy: pancreas (n = 11), small bowel (n = 7), and other (n = 9) neuroendocrine tumors. Overall, 30% (8 of 27) had partial response, 59% (16 of 27) stable disease, and 11% (3 of 27) progressed. Pancreatic neuroendocrine tumors responded differently from small bowel neuroendocrine tumors regardless of cycle number (P = .01). The majority of pancreatic neuroendocrine tumors (6 of 11) had partial response to peptide receptor radionuclide therapy, while all small bowel neuroendocrine tumors had stable disease. Pancreatic neuroendocrine tumors stable after 2 cycles were more likely to respond to additional cycles versus other neuroendocrine tumors (probability: 60% vs 11%).ConclusionPatients with unresectable advanced or metastatic pancreatic neuroendocrine tumors may benefit from a full course of peptide receptor radionuclide therapy, whereas other neuroendocrine tumors appear less likely to respond. Large prospective studies are needed to confirm these findings.     

凉山彝族自治州布拖县2010-2019年抗病毒治疗HIV/AIDS死亡的影响因素分析

目的 分析2010-2019年凉山彝族自治州布拖县抗病毒治疗HIV/AIDS的死亡影响因素,为今后制定可持续的抗病毒治疗策略提供参考依据。方法 采用病例对照研究方法,收集2010-2019年布拖县接受抗病毒治疗HIV/AIDS与死亡者基本和随访信息,按病例数2倍抽样组成对照组,采用logistic回归模型分析其死亡的影响因素。结果 研究对象为抗病毒治疗的HIV/AIDS 3 355例,死亡组1 179例,对照组共2 176例。其中,30~49岁占81.34%,男性占69.09%,彝族占99.55%,已婚或同居占91.12%,初中及以下文化程度占95.77%,农民占88.41%。多因素logistic回归分析结果显示,研究对象的死亡风险因素中,年龄≥50岁是18~29岁的5.08倍（95%CI：3.05~8.48）、女性是男性的0.70倍（95%CI：0.52~0.94）、注射吸毒传播途径是异性性传播途径的1.43倍（95%CI：1.06~1.91）、治疗前CD4⁺T淋巴细胞计数（CD4）≥350个/μl是CD4<200个/μl的0.38倍（95%CI：0.30~0.48）、最近1次使用含洛匹那韦/利托那韦（LPV/r）抗病毒治疗方案是司他夫定（d4T）+拉米夫定（3TC）+奈韦拉平（NVP）/依非韦伦（EFV）方案的0.04倍（95%CI：0.01~0.18）、耐药是不耐药的3.40倍（95%CI：2.13~5.42）,无病毒载量结果且未做耐药检测是不耐药的12.98倍（95%CI：10.28~16.40）。结论 年龄、性别、传播途径、治疗前CD4、最近1次抗病毒治疗方案、抗病毒治疗后耐药检测情况是布拖县接受抗病毒治疗HIV/AIDS的死亡影响因素。应扩大病毒载量和耐药检测覆盖面,科学更换抗病毒治疗方案,开展依从性教育和医务人员培训,降低抗病毒治疗HIV/AIDS死亡率。     

一氧化氮对脊髓和背根神经节神经元的体外存活及活性作用研究

本文应用免疫细胞化学及ＮＳＥ－ＥＬＩＳＡ方法观察了一氧化氮对体外培养脊髓和背根神经节神经元的存活及对活性的影响。结果表明：一氧化氮合酶抑制剂Ｎ－Ａｒｇ组（１００、２００μｍｏｌ／Ｌ）ＮＳＥ免疫反应阳性神经元数目、面积（ＡＦ值）及活性（ＯＤ值）明显大于空白对照组（Ｐ＜０．０１）。而一氧化氮合酶底物Ｌ－Ａｒｇ组（１ｍｍｏｌ／Ｌ）神经元面积积分和活性则小于对照组（Ｐ＜０．０１）。Ｌ－Ａｒｇ的细胞毒性作用可为Ｎ－Ａｒｇ逆转。     

Petal-like apatite formed on the surface of tricalcium phosphate ceramic after soaking in distilled water

In the present study six types of tricalcium phosphate ceramic were prepared and soaked in distilled water for different periods to investigate whether a surface apatite layer was formed on TCP ceramics or not. X-ray diffractometry (XRD) and Fourier-transformed infrared (FTIR) spectrometer were used to examine the changes in crystalline phases and functional groups of TCP ceramics for different soaking periods. Calcium and phosphate ions released from TCP ceramics during soaking were recorded by atomic absorption analysis and ion-coupled plasma. Results revealed that alphaTCP, alphaTCP/betaTCP mixture (alphabetaTCP) and betaTCP ceramic were gradually dissolved. There was no apatite layer formed on their surface after being immersed in distilled water for different durations of time. Mg-TCP ceramic, tricalcium phosphate doped with Mg ions, exhibited a lower dissolution rate than the other types of TCP ceramics. Apatite crystals were also not formed on the surface of Mg-TCP ceramic when immersed in distilled water. Tribasic calcium phosphate, prepared from wet precipitation method, was converted to betaTCP/HAP (HbetaTCP) or alphaTCP/betaTCP/HAP (HalphabetaTCP) crystalline composition at different sintering temperatures (1,150 degrees C and 1,300 degrees C). The surface apatite layer did not appear on HbetaTCP ceramic after soaking. We observed that petal-like apatite was formed on the HalphabetaTCP ceramic surface after being immersed for 2 weeks. alphaTCP phase of HalphabetaTCP ceramic was not directly converted to apatite during soaking. The surface apatite layer formed on the HalphabetaTCP ceramic surface was due to the precipitation of the calcium and phosphate ions released from alphaTCP dissolution. HAP, which existed in the structure of HalphabetaTCP ceramic, plays a role as apatite-precipitating seed to uptake calcium and phosphate ions. TCP ceramics which lacked alphaTCP and HAP content neither converted to apatite nor formed surface apatite on their surfaces during immersion.     

胎盘部位过度反应及胎盘部位结节的临床病理分析

目的探讨胎盘部位过度反应及胎盘部位结节的临床病理学特征以及免疫组织化学染色在鉴别诊断中的意义。方法对15例胎盘部位过度反应及4例胎盘部位结节的临床及病理表现进行回顾性研究,并应用人绒毛膜促性腺激素(hCG)、人胎盘催乳素(hPL)、细胞角蛋白(CK)18、胎盘碱性磷酸酶(PLAP)、α-抑制素(inhibin),进行免疫组织化学染色。结果15例胎盘部位过度反应患者的年龄为25～40岁(平均31．5岁),4例胎盘部位结节患者年龄为26～39岁(平均34．3岁)。15例胎盘部位过度反应的组织学特征为：在子宫内膜、子宫肌层及螺旋动脉中有索条状及片状种植部位中间滋养细胞浸润,子宫内膜及肌层的结构没有破坏。4例胎盘部位结节在子宫内膜组织及变性坏死的绒毛间有多个以致密的嗜酸性玻璃样物质为背景的结节性病变,结节内为绒毛膜型中间滋养细胞。15例胎盘部位过度反应对hPL及CK18均呈阳性反应;4例胎盘部位结节均对CK18、α-抑制素及PLAP均呈阳性反应。所有15例胎盘部位过度反应Ki-67增生指数均≤5％。4例胎盘部位结节Ki-67增生指数均为0。结论胎盘部位过度反应及胎盘部位结节的临床及病理形态学特征不同于滋养细胞肿瘤。免疫组织化学染色对鉴别诊断有帮助。     

Universally conserved and yeast-specific U1 snRNA sequences are important but not essential for U1 snRNP function

To study the contribution of the large, 568-nucleotide yeast (Saccharomyces cerevisiae) U1 snRNA to pre-mRNA splicing, we generated mutations in two regions of the molecule and introduced each mutant gene back into yeast as the sole copy of the U1 snRNA gene. We mutagenized the "A loop," a subregion highly conserved in primary sequence in all U1 snRNA molecules analyzed to date. We also mutagenized a portion of the yeast core subdomain, a region conserved in primary and secondary structure among several yeast species but absent from the much smaller metazoan U1 molecule. Surprisingly, mutations in these two regions had little or no effect on growth rate, yet several of them affected an inefficiently spliced reporter gene construct. In addition, combinations of mutants in both regions gave rise to reduced growth rates. Using the latter assay, we confirmed some of the proposed secondary structure of the yeast core domain. The experiments indicate that both regions contribute to U1 snRNP activity but that mutations in a single region do not have a substantial effect on growth rate because U1 snRNP activity is not rate-limiting for growth.     

绝经后骨质疏松大鼠模型的综合评价

利用双能X线骨密度仪、扫描电镜和骨生物力学试验综合评价大鼠去卵巢后的骨骼状况。结果显示：①大鼠卵巢切除后,活体、离体腰椎以及股骨（除R3区）、胫骨近端干骺端（R1区）的离体骨密度显著下降（P＜0.01),离体L5和L6的骨丢失率最大,达13%;②骨小梁减少、变细,连接中断,骨小梁表面有吸收陷窝;③腰椎压缩强度和股骨力学性均下降,前者更明显,腰椎最大压缩力下降率达33.32%。提示：①类似于绝经后妇女,6月龄大鼠在卵巢切除4个月后骨量和骨质量均下降,特别在富含松质骨的部位,如腰椎、股骨远端等;②利用绝经后骨质疏松大鼠模型评价骨质疏松新药的有效性,应包括该新药对骨量、骨结构和骨强度的作用。     

假鹰爪化学成分研究(Ⅱ)

目的：寻找番荔枝科假鹰爪属植物假鹰爪Ｄｅｓｍｏｓ ｃｈｉｎｅｎｓｉｓ抗肿瘤活性成分。方法：采用硅胶柱色谱分离化学成分。根据理化性质及波谱分析等方法鉴定结构。结果：从氯仿萃取物中分离鉴定了７个化合物,分别是ｕｎｏｎ－ａｌ（Ⅰ）,黄芩素－７－甲醚（Ⅱ）,去甲氧杜鹃花素（Ⅲ）,去甲氧杜鹃花素－７－甲醚（Ⅳ）,苯甲酸（Ⅴ）,β－谷甾醇（Ⅵ）和豆甾醇（Ⅶ）。结论：该种植中鉴定的黄酮类化合物均为β－环未取代,