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.     

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.     

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。     

2008-2018年云南省人间布鲁菌病流行特征及灰色GM(1,1)模型预测

目的分析云南省布鲁菌病(简称布病)流行特征,建立灰色GM(1,1)模型,预测云南省布病病情。方法收集中国疾病预防控制信息系统和云南省统计局2008-2018年云南省布病疫情数据和人口资料,分析布病流行病学特征(包括时间、地区、人群分布),并以灰色GM(1,1)模型进行建模,预测2019、2020年云南省布病发病率。结果2008-2018年云南省共报告布病病例1216例,年均发病率为0.2374/10万,呈逐年递增趋势(χ²趋势=843.34,P<0.01)。病例报告主要集中在3-9月份,占总病例数的69.41%(844/1216)。病例报告数居前5位的州市分别为红河州(289例)、曲靖市(264例)、昆明市(258例)、大理州(160例)、玉溪市(134例),占总病例数的90.87%(1105/1216)。职业以农民为主,占79.03%(961/1216)。建立灰色GM(1,1)模型预测2019、2020年云南省布病发病率分别为0.4876/10万和0.4817/10万。结论云南省布病发病较以往上升,应对重点地区、重点人群进行针对性防控,并对预测结果进行前瞻性评价,逐步完善云南省布病预测模型。     

The prognostic value of platelet-to-lymphocyte ratio on the long-term renal survival in patients with IgA nephropathy

Purpose

Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN).

Methods

We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR?<?15 mL/min/1.73 m², initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients.

Results

330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR?<?106, 106?≤?PLR?≤?137, and PLR?>?137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR?>?137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR?>?137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m².

Conclusions

Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m².

     

Incomplete Administration of Intravenous Vancomycin Prophylaxis is Common and Associated With Increased Infectious Complications After Primary Total Hip and Knee Arthroplasty

BackgroundVancomycin is often used as antimicrobial prophylaxis in patients undergoing total hip or knee arthroplasty. Vancomycin requires longer infusion times to avoid associated side effects. We hypothesized that vancomycin infusion is often started too late and that delayed infusion may predispose patients to increased rates of surgical site infections and prosthetic joint infections.MethodsWe reviewed clinical data for all primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients at our institution between 2013 and 2020 who received intravenous vancomycin as primary perioperative gram-positive antibiotic prophylaxis. We calculated duration of infusion before incision or tourniquet inflation, with a cutoff of 30 minutes defining adequate administration. Patients were divided into two groups: 1) appropriate administration and 2) incomplete administration. Surgical factors and quality outcomes were compared between groups.ResultsWe reviewed 1047 primary THA and TKA patients (524 THAs and 523 TKAs). The indication for intravenous vancomycin usage was allergy (61%), methicillin-resistant staphylococcus aureus colonization (17%), both allergy and colonization (14%), and other (8%). 50.4% of patients began infusion >30 minutes preoperatively (group A), and 49.6% began infusion <30 minutes preoperatively (group B). Group B had significantly higher rates of readmissions for infectious causes (3.6 vs 1.3%, P = .017). This included a statistically significant increase in confirmed prosthetic joint infections (2.2% vs 0.6%, P = .023). Regression analysis confirmed <30 minutes of vancomycin infusion as an independent risk factor for PJI when controlling for comorbidities (OR 5.22, P = .012).ConclusionLate infusion of vancomycin is common and associated with increased rates of infectious causes for readmission and PJI. Preoperative protocols should be created to ensure appropriate vancomycin administration when indicated.     

Emergency Department Observation Versus Readmission Following total Joint Arthroplasty: Can We Avoid the Bundle Buster?

BackgroundAs the Center for Medicare and Medicaid (CMS) moves toward bundled payment plans for total joint arthroplasty (TJA), it becomes necessary to reduce factors that increase cost for an episode of care such as readmissions. The goal of this study is to evaluate the payment for observation stay versus readmission for patients who present to the emergency department.MethodsA retrospective review from 2014-2019 was conducted identifying all Medicare patients who had a primary, elective TJA and visited the ED within 90 days postoperatively. If a readmission was one midnight or less or had an equivalent diagnosis to an observation stay patient, it was characterized as a readmission that could have qualified as an observation stay. Using our institution’s average payment for Medicare readmissions and observations, actual and potential savings were calculated.ResultsSixty-nine out of 523 (13.2%) patients were placed under observation, while 454 (86.8%) patients were readmitted. Eighty-six out of 523 (18.9%) patients qualified for observation status. There was an actual savings of 11.8% by placing patients on observation status and readmission rate was decreased by 13.2%. Savings could have increased by a total of 27.7% and readmissions decreased by a total of 29.6% if all patients who qualified had been placed on observation status.ConclusionAt our institution, the implementation of observation stay has led to a savings of 11.8% and a potential total savings of 27.7%. The rate of readmissions was decreased by 13.2% and had the potential to decrease by a total of 29.6%.