Search

Coal workers' pneumoconiosis (CWP) is a chronic inflammatory and fibrotic pulmonary disease that involves a complex interaction of multiple environmental and genetic factors. Polymorphism, as a genetic factor, may affect the onset of the disease in susceptible populations. The present study investigated the association between the polymorphisms of six genes and CWP risk in a Chinese Han population.Six polymorphisms (CASP8 rs3834129, IL1A rs1800587, IL6 rs1800796, IL4 rs2070874, TNFA rs361525, and NLRP3 rs1539019) were examined in 222 CWP subjects and 247 dust-exposed control subjects.The CASP8 rs3834129 Ins/Del genotype significantly decreased CWP risk (p=0.040; adjusted odds ratio [OR] = 0.586; 95% confidence interval [CI] 0.367-0.935) compared with the Ins/Ins genotype. Stratification analyses revealed a significant interaction between the heterozygous Ins/Del genotype and age. Compared with the Ins/Ins + Del/Del genotype, this was particularly evident among subjects aged 41-60 (p0.001; adjusted OR = 0.054; 95% CI 0.007-0.420) and those with an exposure time of 20-29 years (p=0.014; adjusted OR = 0.392; 95% CI 0.183-0.842). This decreased risk was also found in the group with former smokers (p=0.012; adjusted OR = 0.448; 95% CI 0.238-0.844). Findings revealed that the heterozygous Ins/Del genotype of CASP8 rs3834129 was related to a significantly decreased risk of stage I CWP (p=0.045; adjusted OR = 0.592; 95% CI 0.353-0.992), but not stage II or III CWP.Our study indicated that the heterozygous Ins/Del genotype of CASP8 rs3834129 significantly decreased CWP risk in a Chinese Han population.

UBR5 is recently recognized as a key player in a large number of prevalent cancers. In this study, we sought to explore the connection of UBR5 expression with cell proliferation, apoptosis, as well as the regulation mechanism in colon cancer cell line. SiUBR5 or oeUBR5 were separately applied to interfere the expression of UBR5. Western blot, DNA gel electrophoresis and qPCR were performed to detect the expression of UBR5 at mRNA and protein level. Then MTT and flow cytometry were used to explore the proliferation and apoptosis in a colon cancer cell line in vitro. Finally, we explored the interaction and correlation of UBR5 and P21 in the colon cancer regulation. We found that UBR5 was highly expressed in colon cancer not only at mRNA level but also at protein level. Moreover, UBR5 can promote the growth of colon cancer cells, and inhibit apoptosis. The mechanism exploration proved that UBR5 can degrade P21 via ubiquitination. All these findings suggest that UBR5 may be involved in progression of colon cancer and could be a new therapeutic target for this disease.

目的 分析预处理前多参数流式细胞术（MFC）监测的骨髓微小残留病（MRD）对急性髓系白血病（AML）异基因造血干细胞移植（allo-HSCT）预后的影响，探讨MFC监测MRD在AML allo-HSCT预后评估中的价值。 方法 回顾性分析2012年4月至2015年3月行allo-HSCT的186例AML患者，预处理前骨髓细胞形态学均达第1次完全缓解（CR1）。采用8色MFC对预处理前骨髓进行MRD检测，任何水平异常均定义为MRD阳性。 结果 ①186例AML患者中151例MRD阴性；35例MRD阳性，其中25例MRD

目的 分析NCCN（2015）危险分层对异基因造血干细胞移植（allo-HSCT）治疗的急性髓系白血病（AML）患者预后的影响。 方法 回顾性分析2012年4月至2015年3月完全缓解（CR）后行allo-HSCT治疗的258例AML患者资料（其中186例为CR1，72例为CR2）。按照NCCN（2015）危险分层对患者发病初始进行危险度分层，并分析该分层法对患者预后的影响。 结果 ①258例患者按照NCCN（2015）危险分层法分为低危组63例、中危组112例、高危组83例。中位随访18（5~41）个月，总体2年累积无病生存（DFS）率为78.0%，低、中、高危组分别为78.6%、76.0%、80.3%，三组差异无统计学意义（P=0.886）。②单因素分析结果显示，2年DFS率与NCCN危险分层、移植前病程、发病初WBC数、CR状态、移植前血常规是否恢复正常、移植前染色体是否正常、移植前是否有髓外病变、预处理方案、供者类型、供受者性别、供受者血型、输注的单个核细胞数、输注的CD34+细胞数、输注的CD3+细胞数等无相关性，在继发性AML（P=0.006）及MRD阳性（P=0.003）组患者中明显降低；2年累积复发死亡率在CR2（P=0.046）组患者中明显增高；2年累积非复发死亡（NRM）率在继发性AML（P=0.004）及MRD阳性（P=0.010）组患者中明显增高。③采用Cox回归模型进行多因素分析，结果显示MRD阳性是影响患者2年累积DFS率（HR=2.073，95%CI 1.124~3.822，P=0.020）、NRM率（HR=2.354，95%CI 0.804~6.887，P=0.045）的危险因素。 结论 allo-HSCT治疗CR的AML患者可取得较高疗效，其中CR2与CR1疗效相似；NCCN（2015）危险分层与allo-HSCT治疗的AML患者预后无显著相关性；预处理前多参数流式细胞术监测的MRD状态是影响allo-HSCT治疗的AML患者预后的主要因素。

We have evaluated the effect of feeding ractopamine (Rac), a phenethanolamine lean enhancer being developed for commercial use in finishing pigs, on beta-adrenoceptor (beta-AR) number and ligand-receptor binding affinity in adipose and muscle tissues. Pigs weighing 78 +/- 1 kg were fed Rac (20 mg/kg of diet) for 0 (control), 1, 8, or 24 d before being killed at 105 +/- 1 kg BW. beta-adrenoceptor density (per milligram of protein) was decreased by Rac up to approximately 50% in both the middle and the outer layers of subcutaneous (SQ) adipose tissue. Orthogonal contrasts indicated significant (P < or = .05) linear effects of Rac in middle and outer SQ adipose tissue, and also a significant (P < or = .05) quadratic effect of Rac in the middle layer. Ractopamine did not affect the maximal binding (Bmax) of longissimus muscle. The relative affinity with which the beta-AR population of the tissues examined bound the radioligand ([3H]dihydroalprenolol) was not influenced by Rac. Likewise, feeding Rac had no effect on the affinity of the beta-AR for Rac. The data indicate that a Rac-induced reduction in the Bmax of adipose tissue may account for the diminished in vitro lipolytic potency of exogenous Rac after prolonged periods of Rac feeding, and that Rac-induced desensitization differs between adipose and skeletal muscle tissues.

To determine the temporal effect of ractopamine (Rac), a phenethanolamine, on adipose lipogenic enzyme activity and gene expression, 20 crossbred barrows were fed Rac (20 mg/kg of diet) for 0, 1, 8, or 24 d before slaughter (105 +/- 1 kg). Ractopamine had no effect (P > .05) on the activity of acetyl-coenzyme A carboxylase or malic enzyme in either the middle or outer layers of subcutaneous adipose tissue. Similarly, mRNA abundance for acetyl-coenzyme A carboxylase and the glucose transport proteins Glut 1 and Glut 4 were not affected by Rac in either adipose depot. Despite the inability of Rac to affect adipose tissue metabolism, Rac increased nitrogen retention, longissimus muscle area, and alpha-actin gene expression in skeletal muscle. Results indicate that Rac was not a functional beta-adrenergic agonist toward adipose tissue in this study. We suggest that the response to Rac in adipose tissue is masked by a combination of factors including tissue insensitivity, Rac-dose limitation, inherent partial agonism of Rac, and beta-adrenoceptor down-regulation.

The measurement of CA50 in serum and pleural fluid by immunoradiometric assay was presented in 45 (27 malignancy and 18 tuberculosis) patients with pleural effusion. The mean CA50 level in malignant effusion (89.26 +/- 122.32 U ml-1) was significantly higher than that in tuberculous effusion (5.18 +/- 8.65 U ml-1) (P < 0.001). CA50 levels of pleural fluid above an arbitrary level of 20 U ml-1 were found in 78% of malignant fluids and in 6% of tuberculous fluids. The serum CA50 value from 27 patients with malignant effusion (58.67 +/- 85.85 U ml-1) was also higher than that from 18 patients with tuberculous effusion (6.18 +/- 8.37 U ml-1) (P < 0.001). CA50 levels of serum above the same level were found in 58% of patients with malignant fluid and in 6% of patients with tuberculous fluid. The results suggested that the measurement of CA50 in pleural effusion may be helpful in the differential diagnosis between tuberculous and malignant effusions.

Graft-versus-host disease (GVHD) and infection are major obstacles to successful allogeneic bone marrow transplantation (allo-BMT). In an attempt to improve the results of HLA-identical sibling BMT, we investigated the effect of accelerating hemopoietic reconstitution and reducing acute GVHD (aGVHD) in allo-BMT receiving G-CSF-stimulated donor marrow and the preliminary biological mechanism. The donors of 30 patients (study group) with leukemia were given G-CSF 3-4 microg/kg/d for 7 doses prior to marrow harvest. The results of subsequent engraftment in the recipients were compared with those of 18 patients without G-CSF (control group). Five donors themselves were studied to assess the effects of G-CSF on the hematopoietic progenitor cells and lymphocyte subsets in the bone marrow (BM). We observed that the stimulated BM yielded higher numbers of nucleated cells as well as CFU-GM and CD34+ cells (p0.01), and that hemopoietic reconstitution was accelerated. The median number of days of granulocyte count exceeding 0.5x10(9)/L and platelet count exceeding 20x10(9)/L was 16 (range 10-23 d) and 18.5 (range 13-31 d), respectively (control group: median 22 d, range 13-29 d and median 23 d, range 17-34 d; p=0.001). The incidence of grade II-IV severe aGVHD was very low, with only 1 case (3.3%) with acute grade II aGVHD limited to the skin in the study group. Five of 18 patients in the control group manifested grade II-IV severe aGVHD (27.8%, p=0.02). The number of T-lymphocyte subsets in the harvested BM using G-CSF stimulation was changed. In the G-CSF-stimulated marrow group, CD4+ decreased and CD8+ increased significantly (p=0.02). The changes of progenitor cells and T-lymphocyte subsets in donors' BM from pre- and post-G-CSF stimulation showed that the percentage of CD4+ reduced (p=0.04) and that of CD8+ increased (p=0.06), while that of CD34+ also increased (p=0.002). The incidence of chronic GVHD and relapse had no significant difference between both groups. These results indicate that allo-BMT in BM G-CSF priming can accelerate engraftment and minimize the incidence of severe aGVHD. There is a trend in favor of improved transplantation-related mortality.

The hormone-sensitive and lipoprotein lipases are critical determinants of the metabolic adaptation to starvation. Additionally, the uncoupling proteins have emerged with potential roles in the metabolic adaptations required by energy deficiency. The objective of this study was to evaluate the expression (mRNA abundance) of uncoupling proteins 2 and 3 and that of hormone-sensitive and lipoprotein lipase in the adipose tissue and skeletal muscle of the pig in relationship to feed deprivation. Thirty-two male castrates (87 kg +/- 5%) were assigned at random to fed and feed-deprived treatment groups. After 96 hr, the pigs were euthanized and adipose and skeletal muscle tissue obtained for total RNA extraction and nuclease protection assays. Feed deprivation increased uncoupling protein 3 mRNA abundance 103-237% (P0.01) in longissimus and red and white semitendinosus muscle. In contrast, the increase in uncoupling protein 3 mRNA in adipose tissue was only 23% (P0.06), and adipose uncoupling protein 2 mRNA was not influenced (P0.66) by feed deprivation. The increased abundance of uncoupling protein 2 mRNA in the longissimus muscle of feed-deprived pigs was small (22%), but significant (P0.04). The expression of hormone-sensitive lipase was increased 46% and 64% (P0.04) in adipose tissue and longissimus muscle, respectively, by feed deprivation, whereas adipose lipoprotein lipase expression was reduced (P0.01) to 20% of that of the fed group. Longissimus lipoprotein lipase expression in the feed-deprived group was 37% of that of the fed group (P0.01), and similar reductions were detected in red and white semitendinosus muscle. Overall, these findings indicate that uncoupling protein 3 expression in skeletal muscle is quite sensitive to starvation in the pig, whereas uncoupling protein 2 changes are minimal. Furthermore, we conclude that hormone-sensitive lipase is upregulated at the mRNA level with prolonged feed deprivation, whereas lipoprotein lipase is downregulated.

Localization of ferritin with immunohistochemical staining was carried out in thirty six cases of malignant histiocytosis (MH). The positivity rate for ferritin was 100 per cent. Ferritin was found to exist in the cytoplasm of the tumor cells. Image analysis showed that ferritin level in the well-differentiated histiocytes (1.2314) was higher than that in the atypical histiocytes (0.7181) (P0.01). Ten MH patients showed surprising high serum ferritin concentration (1482.3 ng/ml) than that in normal. Our data suggest that ferritin is the tumor associated antigen in MH. The synthesis and release of ferritin by MH tumor cells is the important cause for the high concentration of serum ferritin in patients.

21 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 3 patients with Evan's syndrome underwent partial splenic embolization (PSE). 22 patients underwent PSE once, while 2 patients were treated twice, thus a total of 26 procedures were carried out. Follow-up 3 months after embolization was available in all the 24 patients for their response to embolization therapy. 16 patients (67%) achieved complete remission (platelets greater than 100 x 10(9)/L) and 4 (17%) partial remission (platelets greater than 84 x 10(9)/L) after splenic embolization. A total efficacy rate of 83% was observed. This response to embolization after transcatheter vessel occlusion 3 months after is similar to the reported results of splenectomy. Not only may the morbidity and mortality associated with surgical splenectomy be avoided, but also the noninfarcted spleen may continue to provide immunologic functions. The most important experience in this series, however, was the emphasis on partial (60-70%) rather than total splenic arterial embolization. The sequestration site of platelets was associated with the outcome of splenic embolization. More splenic sequestration sites were found in responders, to the therapy.

Seven-day-old primary myotube cultures derived from embryonic chicken limb muscles were used to determine the effects of the beta-adrenergic agonist isoproterenol (ISO) on muscle protein metabolism in vitro. Isoproterenol increased (P less than .05) total protein accumulation after 2 h of acute exposure and after chronic exposure for 24 and 48 h. Isoproterenol did not consistently retard rate of protein degradation of the total protein (TP), myofibrillar protein (MFP) pools, and myosin heavy-chain subunit (MHC); degradation of these protein pools tended to be slowed by inclusion of ISO in the culture medium. After acute treatment of 1 X 10(-4) M ISO for 2 h, TP, but not MFP and MHC, synthesis rate was increased, and after chronic exposure to 1 X 10(-4), 1 X 10(-5), and 1 X 10(-6) M ISO, TP, MFP, and MHC synthesis rates and net accumulation of TP, cytoplasmic protein, and MHC fractions were enhanced (P less than .05). The beta-adrenergic antagonist propranolol (1 X 10(-5) M) blocked chronic stimulatory effects of ISO. Furthermore, after 48 h of exposure to ISO, effects on protein synthesis were less pronounced than those observed after 24 h of exposure. Isoproterenol imparted a more pronounced effect on protein synthesis than on protein degradation, indicating that increased muscle protein accretion observed in animals after ISO treatment is likely a function of enhanced protein synthesis.

Substances in evacuated blood-collection devices produce gas-chromatographic peaks with retention times similar to those of drugs. All tubes tested except the serum separator tubes contained tris(2-butoxyethyl) phosphate, as determined by mass spectrometry. In addition, the partition coefficient during the solvent-extraction step increased for some drugs by as much as 40%, while for other drugs it decreased by as much as 30%, depending on the drug and the collection tube. The Becton Dickinson serum separator tube also contains several other compounds identified by mass spectrometry to be dibasic esters used in the preparation of the polyester gel. The Corning serum separator tube and the Venoject serum tube contain still other impurities. The Becton Dickinson royal-blue-stoppered tube contained the least amount of impurities of the tubes tested. CVs of 25 commonly measured drugs in plasma pools increased from 5% for samples collected in glass tubes to greater than 20% for samples collected in evacuated blood-collection tubes. Clearly, accuracy and precision of measurements of therapeutic drugs can be seriously compromised if an inappropriate blood-collection device is used.

Substances in evacuated blood-collection devices produce gas-chromatographic peaks with retention times similar to those of drugs. All tubes tested except the serum separator tubes contained tris(2-butoxyethyl) phosphate, as determined by mass spectrometry. In addition, the partition coefficient during the solvent-extraction step increased for some drugs by as much as 40%, while for other drugs it decreased by as much as 30%, depending on the drug and the collection tube. The Becton Dickinson serum separator tube also contains several other compounds identified by mass spectrometry to be dibasic esters used in the preparation of the polyester gel. The Corning serum separator tube and the Venoject serum tube contain still other impurities. The Becton Dickinson royal-blue-stoppered tube contained the least amount of impurities of the tubes tested. CVs of 25 commonly measured drugs in plasma pools increased from 5% for samples collected in glass tubes to greater than 20% for samples collected in evacuated blood-collection tubes. Clearly, accuracy and precision of measurements of therapeutic drugs can be seriously compromised if an inappropriate blood-collection device is used.

Fourteen patients with severe aplastic anemia were treated with antilymphocyte globulin (ALG). Eight were studied with co-culture of patient's lymphocytes with normal bone marrow cells. Suppression of CFU-C was prevented by pretreatment of T lymphocytes with anti-T lymphocyte McAb in four patients and concordance with clinical outcome was observed only in two patients. Conclusive in vivo therapy result for this correspondence are lacking. Seven patients received fetal liver cell suspension infusion 24-36 hours after completing ALG therapy and remission were "more complete" in three cases with good response. Response of treatment in the fourteen patients was as follows: eight had complete or partial responses and the remaining did not respond or died (42.8%).