Dissecting the biological heterogeneity of HER2-positive breast cancer

HER2-positive (HER2+) breast cancer (BC) is a heterogenous and multifaceted disease, with interesting therapeutic implications. First, all intrinsic molecular subtypes can be identified in HER2+ tumors, with the HER2-enriched being the most frequent. Such subtypes do not differ much from their counterparts in HER2-negative disease, apart for the high expression of genes in/near the HER2 amplicon on chromosome 17. Intrinsic subtyping, along with the quantification of ERBB2 mRNA levels, is associated with higher rates of pathologic complete response across neoadjuvant trials of dual HER2 blockade and might help select patients for de-escalation and escalation treatment strategies. Secondly, HER2+ tumors have a broad range of DNA alterations. ERBB2 mutations and alterations in the PI3K/Akt/mTOR pathway are among the most frequent and might predict benefit from potent pan-HER, PI3K and mTOR inhibitors. Moreover, HER2+ tumors are usually infiltrated by lymphocytes. These tumor infiltrating-lymphocytes (TILs) predict response to neoadjuvant anti-HER2-based treatment and exert a prognostic role. PD-L1, detected in ∼42 % of HER2+ BC, might also be useful to define patients responding to novel anti-PD1/PD-L1 immunotherapies. New multiparametric clinicopathologic and genomic tools accounting for this complexity, such as HER2DX, are under development to define more tailored treatment approaches. Finally, HER2-targeted antibody-drug conjugates (ADC) such as trastuzumab deruxtecan might be active in tumors with low expression of HER2. Overall, there is a need to molecularly characterize and develop novel targeted therapies for HER2+ disease.     

电灼结合中药内服外洗治疗尖锐湿疣的疗效观察

目的观察电灼结合中药内服外洗治疗尖锐湿疣的临床疗效及对患者T淋巴细胞亚群的影响。方法选择从2013年7月至2017年11月山西医科大学附属大同市第三人民医院泌尿外科治疗尖锐湿疣的患者148例,随机分成对照组和观察组两组,每组74例。对照组患者单独采用电灼治疗;观察组患者在采用电灼基础上结合中药内服外洗共同治疗。结果观察组尖锐湿疣患者复发率为10.8%,低于对照组尖锐湿疣患者复发率28.4%,差异具有统计学意义。(P<0.01)。两组治疗后复发组CD3+细胞、CD4+细胞水平、CD4+/CD8+细胞比值较未复发组低,而CD8+细胞水平较未复发组高,差异具有统计学意义。(P<0.05)。治疗后,观察组尖锐湿疣患者CD3+水平、CD4+水平、CD4+/CD8+比值高于对照组尖锐湿疣患者,且观察组尖锐湿疣患者CD8+水平低于对照组尖锐湿疣患者CD8+水平,差异具有统计学意义(P<0.01)。结论电灼结合中药内服外洗能减少尖锐湿疣的复发率。在临床治疗中,监测尖锐湿疣患者外周血T淋巴细胞亚群,对尖锐湿疣患者治疗后的复发预估及相应增强免疫治疗具有重要的指导意义。     

Changes in T .lymphocyte subsets after severe traumatic brain inJury

BACKGROUND： Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE： To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN： A comparative observation. SETTINGS： Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS： All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People＇s Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score （GCS） was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group （GCS ranged 14- 15 points）, including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS： （1） The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. （2） The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES： Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS： Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. （1） Changes of T lymphocyte subsets： At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group （t =2.77 - 3.26, P 〈 0.01）, and began to recover at 7 days, which were significantly different from those in the control group （t = 2.06 - 2.24, P 〈 0.05）, and generally recovered to the normal levels at 14 days （P 〉 0.05）. （2） Conditions of pulmonary infections： At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% （22/30）, 0, x2=37.29, P 〈 0.01]. CONCLUSION： Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period （within 7 days）, and they are easily to be accompanied by pulmonary infections.     

胸腺肽α1对老年晚期恶性肿瘤患者细胞免疫功能的影响

目的 :观察胸腺肽α1对老年恶性肿瘤患者细胞免疫功能的影响。方法 :30例老年恶性肿瘤患者 ,用胸腺肽α1治疗 2个月 ,第 1个月每日 1.6 mg,第 2个月隔日 1.6 mg,均为皮下注射 ,观察治疗前后 T细胞亚群及 NK细胞、患者生活质量、血常规及肝肾功能变化。结果 :30例患者用胸腺肽α1前 ,CD4、CD4 /CD8、NK细胞分别为 (32 .33± 6 .2 5 ) %、(0 .77± 0 .2 3) %、(16 .0 5± 6 .79) % ,治疗后为 (39.4 2± 9.2 6 ) %、(1.19± 0 .5 3) %、(2 4 .37± 8.2 3) %。治疗前后比较均有显著意义 (P<0 .0 5 ) ,患者生活质量分值治疗后比治疗前显著提高 (P<0 .0 5 )。结论 :胸腺肽α1能提高老年晚期恶性肿瘤患者的细胞免疫功能 ,是较理想的免疫增强剂。     

急性高容量性血液稀释对妇科肿瘤患者围术期T淋巴细胞亚群的影响

目的探讨急性高容量性血液稀释(AHH)对妇科肿瘤患者围手术期T淋巴细胞亚群的影响.方法40例ASAⅠ～Ⅱ级的妇科肿瘤手术病人随机分成两组:高容量性血液稀释组(A组)在切皮前30分钟内输入6%羟乙基淀粉液1000ml;对照组(C组)常规输液,不实施血液稀释.分别与麻醉诱导前、手术结束后、术后24小时抽取静脉血,用流式细胞仪测定T淋巴细胞亚群CD3 、CD4 、CD8 及CD4 /CD8 细胞百分率.结果两组病人手术结束后(T1)、手术后第1天(T2)与麻醉诱导前(T0)比较:T淋巴细胞亚群CD3 、CD4 及CD4 CD8 均明显降低(P＜0.01或P＜0.05),CD8 无显著性变化;但A组手术结束后和手术后第1天CD3 、CD4 及CD4 /CD8 明显高于C组(P＜0.05).结论术前采用急性高容量性血液稀释(AHH),可显著改善妇科肿瘤患者T淋巴细胞的免疫功能.     

HLA-B*27 subtyping by PCR-RFLP in Spanish patients with ankylosing spondyiitis

Abstract: We describe the use of restriction analysis on PCR-amplified DNA for detecting all B*27 subtypes except B*2710 and B*2711 (i.e. from B*2701 to B*2709). After detecting B*27 by Sty I, double digestions consisting of Sty I plus another informative enzyme led to subtype assignment. We used mismatched primers to create restriction sites when necessary. The method avoids group-specific amplifications and other laborious optimization procedures. It was successfully tested on a panel of well characterized cell lines covering different B*27 subtypes. Then, we studied a group of 57 ankylosing spondyiitis patients and 746 controls from the south of Spain. B*27 showed a very strong association with the disease (OR=211.27, P=\0˜7). B*2702 and B*2705 distribution in controls (20% and 77.1%, respectively) differed from previously reported data in the Spanish population. We unexpectedly found the B*2707 allele in our population (one control).     

Prognostic implications of the motor symptoms of Parkinson's disease with respect to clinical,computertomographic and psychometric parameters

Summary Forty-four Parkinson patients (19 patients of the rigid-akinetic type, 13, of the rigid-akinetic-tremor type, and 12, of the tremor type) were included in a study in order to analyse correlations of the expression of the motor symptoms tremor, rigidity, akinesia, with other clinical parameters, computertomographic aspect of brain atrophy and psychometrically assessed cognitive parameters. Rigidity and akinesia are significantly positively correlated with the severity of motor dysability, stage of the disease, and brain atrophy, as is akinesia with a history of pharmacotoxic psychosis. Tremor is significantly negatively correlated with motor dysability, stage of the disease, and history of pharmacotoxic psychosis. Akinesia is correlated with visuomotor dysfunction (tested with Bender Gestalt Test) and rigidity with the depression score (Zung scale). The tremor type is favorable, the rigid-akinetic type unfavorable with respect to motor disability and psychosis.     

A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

Polysaccharidenucleicacidfractionofbacilluscalmetteguerin (BCG PSN ,SiqikangInjection)andthymopeptidesarenowtwowidelyusedimmunomod ulatorsinclinicalpractice .Theyareusuallyusedasanadjuvanttherapyforvirusinfection ,autoimmunediseasesandneoplasms ,whichhavebeenclinicallyprovedtobeeffective .Somereportsdemonstratedthattheybothcanstimulatetheproliferationanddif ferentiationofT lymphocytes.However ,theexactmechanismshavenotbeenelucidatedyet .InordertocomparetheirmodulatingmechanismsonT lympho c…     

分次照射对兔外周血T淋巴细胞DNA合成影响动态观察

本文对长耳白兔受一次与分次~(60)Cor线不同剂量照射后一个月内其外周血T淋巴细胞DNA合成率进行了连续观察。结果表明一次性照射各剂量组均在照后第1天DNA合成受抑最严重;照后第3天各组开始恢复;第7天各组均恢复到照前水平。在分次照射停照后1.0Gy组不但未下降反而有升高趋势。当剂量率、累积剂量均相同,仅分割次数不同时发现0.05Gy/d组受抑程度比0.10Gy/d组明显。