Possibilities of interference with the immune system of tumor bearers by non-lymphoid Fc gamma RII expressing tumor cells.

The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested.     

Tumour-bound immunoglobulins. The in vitro disappearance of immunoglobulin from the surface of coated tumour cells, and some properties of released components

Immunoglobulin-coated ascites tumour cells lose some of their immunoglobulin coat following their transfer to in vitro culture conditions. The uncoating process is metabolism-dependent and related to the turning over of cell-surface components.     

125I-白细胞介素-8在小鼠体内的分布研究

为了解白细胞介素 - 8的体内行为 ,用 Bolton- Hunter法对 IL- 8进行 1 2 5I标记 ,并测定它在小鼠体内的分布 ;得到了 1 2 5I- IL- 8在小鼠血、心、肝、肺、肾、骨、脾等脏器中的分布以及它在血液中的快相半排期 T1 /2α为 0 .3 2 h和慢相半排期 T1 /2β为 8.0 1h。1 2 5I- IL- 8主要通过肾排除     

Secondary sulphonylurea failure: what pathogenesis is responsible?

Sulphonylurea (SU) stimulates insulin secretion by pancreatic beta-cells and is generally used as a first-line treatment for type 2 diabetes. However, after long-term SU treatment (six months or over), some patients begin to show an increase in blood glucose once again (secondary SU failure). Two theories have been put forward to explain this failure--dysfunction of the proinsulin conversion machinery or insulin resistance. However, the primary pathogenesis behind secondary SU failure still needs to be investigated. Using a reliable technique that specifically identifies intact proinsulin (IPI), total proinsulin (TPI) and specific insulin (SI), this study aims to discover if a defect in the proinsulin converting mechanism plays a role in SU failure. Three groups were recruited for this study: healthy controls (n=8), SU responders (n=38) and secondary SU failures (n= 46). Serum concentrations of insulin-related molecules released in response to a standard glucose challenge test were compared between the groups. It was found that total SI was lower in the patient groups (P<0.05 compared to the control group), while TPI and IPI showed no distinct difference between the three groups (P>0.05). TPI:SI ratio and IPI:SI ratio showed marked increases in the patient groups (P<0.05 compared to control group), with no obvious quantitative difference between SU responders and secondary SU failures (P>0.05). Similar results for the Homa Insulin Resistant Index were found between the two patient groups. Interestingly, blood glucose at 180 mins after glucose challenge was significantly higher in the secondary SU failure group (P<0.05), with no correlation to SI, while the SU responder group showed good correlation between the parameters (P<0.05). We conclude that type 2 diabetes is associated with obvious dysfunction in the proinsulin-converting process and shows severe SI deficiency in responding to glucose challenge. Dysfunction of the proinsulin conversion mechanism was not an extra cause responsible for SU failure.     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

Altered expression of G1 regulatory proteins in human soft tissue sarcomas

CONTEXT: Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited. OBJECTIVES: To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior. DESIGN: The p53 and Rb-cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively. RESULTS: Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb-cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse. CONCLUSION: Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb-cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb-cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.     

Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes

Progressive deterioration of beta-cell function is proposed as a disease-related factor of sulphonylurea (SU) failure in type 2 diabetes. If it gradually worsens over time then disease duration may mirror the progressive beta-cell deterioration. The aim of the present study is to assess whether or not disease duration is influential in remodelling the secretion pattern of insulin-like molecules and in glucose control of SU-treated type 2 diabetes. A research model is used to investigate proinsulin secreting capacity over time, using two groups of patients: i) disease duration <5 years (n=62), comprising SU responders (SUr; n=48) and SU failures (SUf; n=14); and ii) disease duration > or = 5 years (n= 37), comprising an SUr group (n=17) and an SUf group (n=20). Blood samples are taken at 0 h, 0.5 h 1 h, 2 h and 3 h during a standard oral glucose tolerance test and measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI) concentrations. Pairwise comparison of estimated marginal means of blood glucose, SI, IPI and TPI levels at each time point are carried out between groups and subgroups. (SUr vs. SUf). Homa insulin resistance index (IR index) is applied to analyse IR between the groups. It was found that patients with shorter disease duration had higher proinsulin (TPI and IPI) levels at all time points (P<0.05), together with a lower glucose level at 2 h and 3 h (P<0.05). Homa insulin index analysis showed no difference between the two groups (P=0.26). Results also showed that the SUr group had a significantly lower glucose level at Oh and 3h (P<0.05), although no significant difference in insulin and proinsulin levels was found between the SUr and SUf groups. In conclusion, proinsulin may play an important role in glucose control in SU-treated type 2 diabetes, but the effect is reduced in SUf patients.     

颅脑肿瘤术后并发静脉血栓栓塞症危险因素的Meta分析

目的明确颅脑肿瘤术后患者发生静脉血栓栓塞症(VTE)的危险因素。方法检索中国知网、万方、维普、中国生物医学文献、PubMed、The Cochrane Library、Web of Science、EMbase等数据库建库至2021年11月1日颅脑肿瘤术VTE危险因素的队列研究或病例对照研究。由两名研究人员独立进行文献筛选、资料提取以及文献质量评价。使用RevMan 5.4软件对纳入文献进行Meta分析。结果共纳入14篇文献,合计样本量40 552例,发生VTE1 801例。Meta分析结果显示,年龄＞45岁、术前D-二聚体升高、肥胖、女性、术前日常生活活动能力处于依赖状态、术前呼吸机依赖、术前曾患脓毒血症、高级神经胶质瘤、手术时间＞3.05 h、术后D-二聚体升高、术后下肢运动功能障碍、术后卧床不起、术后并发尿路感染为颅脑肿瘤术后患者发生VTE的危险因素。结论颅脑肿瘤术后VTE发生与多种因素有关。建议构建颅脑肿瘤术后VTE风险预测模型,关注高风险人群,落实规范化静脉血栓风险评估,注重血栓评估过程管控。     

推进全球公共卫生治理建设的挑战与思考

新型冠状病毒肺炎疫情极大威胁了人类健康和全球公共卫生安全,严重破坏了各国的卫生健康系统,加剧了全球卫生健康的系统性不公平,进而导致了可持续发展目标进展缓慢甚至逆转,由此凸显了推进全球公共卫生治理建设的紧迫性。目前,全球公共卫生治理面临诸多挑战,如治理共同体的理念尚未得到普遍共识,治理结构的领导权威缺位,治理机制的效率低下,公共卫生信息监测系统的数字鸿沟明显等。为此,建议从以下5个方面推进全球公共卫生治理建设：加快构建人类卫生健康命运共同体,加快全球公共卫生治理机制的构建和完善,确保全球公共卫生产品供给的公平和可及,重塑全球公共卫生治理结构的领导体系,弥合全球公共卫生信息监测能力的差距。     

科技期刊邮件推送的用户调研与策略分析

【目的】 从读者和期刊两方面进行调研,对比分析科技期刊通过邮件推送进行宣传,从而促进学术成果有效传播,增强用户黏性的策略,为我国科技期刊宣传提供参考。【方法】 通过问卷调查、实例调研、案例分析及对比,分析不同做法对邮件推送结果的影响,给出优化的方法和建议。【结果】 问卷调研结果反映的用户需求与同行期刊和中国激光杂志社邮件推送实例的分析结果相互印证。科技期刊在进行邮件推送时,要先了解邮件推送目标用户的需求,并根据需求对邮件推送活动进行合理优化。【结论】 精准性是邮件推送工作首先要考虑的因素;合适的主题、时效性强、恰当的推送频率也是推送工作需注意的要素。