Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model

Background Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.Methods Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1–11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.Results Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.Conclusion Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.This study was financially supported by a grant from Ortho Biotech, a division of Janssen Cilag, Tilburg, the Netherlands     

Global vascular expression of murine CD34, a sialomucin-like endothelial ligand for L-selectin

Extravasation of leukocytes into organized lymphoid tissues and into sites of inflammation is critical to immune surveillance. Leukocyte migration to peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and Peyer's patches (PP) depends on L-selectin, which recognizes carbohydrate-bearing, sialomucin-like endothelial cell surface glycoproteins. Two of these ligands have been identified at the molecular level. One is the potentially soluble mucin, GlyCAM 1, which is almost exclusively produced by high endothelial venules (HEV) of PLN and MLN. The second HEV ligand for L-selectin is the membrane-bound sialomucin CD34. Historically, this molecule has been successfully used to purify human pluripotent bone marrow stem cells, and limited data suggest that human CD34 is present on the vascular endothelium of several organs. Here we describe a comprehensive analysis of the vascular expression of CD34 in murine tissues using a highly specific antimurine CD34 polyclonal antibody. CD34 was detected on vessels in all organs examined and was expressed during pancreatic and skin inflammatory episodes. A subset of HEV-like vessels in the inflamed pancreas of nonobese diabetic (NOD) mice are positive for both CD34 and GlyCAM 1, and bind to an L-selectin/immunoglobulin G (IgG) chimeric probe. Finally, we found that CD34 is present on vessels of deafferentiated PLN, despite the fact that these vessels are no longer able to interact with L-selectin or support lymphocyte binding in vitro or trafficking in vivo. Our data suggest that the regulation of posttranslational carbohydrate modifications of CD34 is critical in determining its capability to act as an L-selectin ligand. Based on its ubiquitous expression, we propose that an appropriately glycosylated form of vascular CD34 may act as a ligand for L-selectin-mediated leukocyte trafficking to both lymphoid and nonlymphoid sites.     

Asthma caused by potassium aluminium tetrafluoride: a case series

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF₄)-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF₄ − with fluorides’ workplace air concentrations ranging between 1.7 and 2.8 mg/m³. No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients’ exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation.     

腹腔镜手术对不孕症患者的诊断及治疗价值研究

目的探讨腹腔镜手术对不孕症患者的诊断及治疗价值。方法回顾性分析新疆医科大学第一附属医院2010年9月-2014年5月收治的319例不孕症患者的临床资料,对所有患者行腹腔镜下诊断及相应的手术治疗(包括盆腔粘连分解、输卵管造口术、输卵管灼断术等)。结果 319例患者腹腔镜术中检查与术前子宫输卵管碘油造影结果的符合率为72.1%(230/319),其中有43例术中发现子宫肌瘤,56例术中发现输卵管系膜囊肿,8例患者术中发现子宫内膜异位症,有2例患者诊断为盆腔结核,1例术中发现结肠肌瘤(术前考虑卵巢囊肿),其余为不同程度的盆腔慢性炎症。轻度粘连69例,妊娠21例,宫外孕2例,妊娠率33.33%。中重度粘连250例,其中行灼断术34例,灼断术患者后行体外受精及胚胎移植(IVF-ET),妊娠13例,妊娠率38.23%(13/34)。其余216例,失访3例,妊娠31例,宫外孕3例、妊娠率15.9%。结论腹腔镜对诊断输卵管性不孕及盆腔疾病有重要价值,子宫输卵管造影仅能初级筛查,诊断价值有限。在治疗输卵管粘连梗阻中,腹腔镜的治疗价值有待进一步探讨,临床预后与盆腔炎症的程度有关,应个体化选择手术方案。     

Successful treatment of COVID-19 infection with convalescent plasma in B-cell-depleted patients may promote cellular immunity

Treatment with convalescent plasma has been shown to be safe in coronavirus disease in 2019 (COVID-19) infection, although efficacy reported in immunocompetent patients varies. Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody-producing B cells, such as those treated with rituximab (anti-CD20) for hematological malignancies, lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analyzed clinical course and inflammation markers of three B-cell-depleted patients suffering from COVID-19 who were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA-DR-positive T-cells ex vivo and CD137-positive T-cells after in vitro stimulation with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137-positive T-cells after stimulation with SARS-CoV-2 peptides showed an increase in peptide-specific T-cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B-cell-depleted patients and present data that suggest that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T-cell responses.     

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971     

TLIF术式在布氏杆菌性脊柱炎病人中的临床疗效及安全性分析

目的 对比分析单纯后路内固定+一期经腰椎间孔病椎间病灶清除(TLIF)与经典的前后联合手术在布氏杆菌性脊柱炎患者中的临床疗效及安全性。 方法 对我院2015年1月至2017年12月收治的93例布病性脊柱炎患者的临床资料进行分析。按手术方式分为观察组(45例)和对照组(48例)。对两组患者的基础数据、临床指标、术前术后各项指标水平以及术后并发症、植骨治愈情况。 结果 观察组与对照组基础数据比较,差异无统计学意义(P>0.05)。观察组患者的手术时间、住院天数、术中出血量及术后下床时间均明显低于对照组(P<0.01)。两组患者术后3个月的ODI、VAS、CRP、ESR及Cobb角均明显低于术前(P<0.05);术后3个月,观察组患者的ODI、VAS、CRP、ESR及Cobb角均明显低于对照组(P<0.05)。观察组术后并发症发生率(4.4%)明显低于对照组(25.0%)(Χ²=7.674,P<0.01)。 结论 TLIF治疗布氏杆菌性脊柱炎患者的临床疗效突出,安全性较好,更有利于患者术后身体的恢复。