italic>γ-Aminobutyric acid (GABA) is a crucial inhibitory neurotransmitter found in various cells in the human body. While the GABAergic system is typically associated with the nervous system, recent research has revealed that immune cells and tumor cells also express components of this system. In the tumor microenvironment (TME), GABA is secreted to act extracellularly on other cells. GABA is metabolized via the GABA shunt and is involved in the tricarboxylic acid (TCA) cycle by generating succinate, which can provide energy for tumor cells. Activation of GABA receptors (GABARs) is a major pathway through which GABA participates in the regulation of antitumor immune responses. The activation of GABA type A receptors (GABA_ARs) can inhibit the activation and proliferation of T cells, elicit anti-inflammatory macrophages, and promote tumor cell growth and migration, while activation of GABA type B receptors (GABA_BRs) is generally considered to inhibit cancer cell migration and induce cancer cell apoptosis. In general, receptor activation inhibits immune cells, but the effect on tumor cells varies. Additionally, the downregulation of the expression levels of GABA transporters (GATs) is involved in tumor progression. Although antagonists of GABA metabolism and drugs that act on GABA receptors are considered therapeutic drugs for tumors, there have been few clinical studies conducted on them.

Objective To evaluate the impact of total parenteral nutrition(TPN)on nutrition status and inflammatory markers in hospitalized fasted patients with inflammatory bowel disease(IBD).Methods A retrospective study was performed and 82 hospitalized fasted IBD patients [male/female=58/24,(39.4±14.5)years] who received TPN entered the study.Among them,38 patients had ulcerative colitis(UC)and 44 patients suffered from Crohn`s disease(CD).Clinical data(gender,age,duration of disease,history of disease,prednisone,immuno-suppressor,and antibiotics)were obtained from medical records.Nutritional parameters,C-creative protein(CRP),and erythrocyte sedimentation rate(ESR)before and after TPN were also obtained.Average caloric supplementation by TPN was(4 437.3±1 199.1)kJ/d and the nitrogen amount was(9.9±1.7)g/d.Median PN length was 15 days(7-54 days).67 IBD patients received a TPN formula with glutamine(≥14 d,25 patients vs.0-14 d,42 patients)and 15 IBD subjects received TPN without glutamine.Malnutrition was diagnosed by body mass index(BMI)and serum albumin level.Results The prevalence of undernutrition was 90.2％(74/82)in the study population.CD patients had a significantly longer history of disease [84(3-288)months vs.24(1-324)months,P<0.001] and a significantly lower BMI [(15.6±1.8)kg/m2 vs.(19.1±3.5)kg/m2,P<0.001] compared with those in UC patients.TPN improved nutritional parameters [serum albumin:(28.7±6.6)g/L before TPN vs.(31.7±5.8)g/L after TPN,P<0.001;pre-albumin:(174.1±85.5)mg/L before TPN vs.(227.2±82.8)mg/L after TPN,P<0.001].Conclusions TPN improves nutritional status in hospitalized fasted IBD patients.However,prospective randomized controlled trials are required to estimate the role of low-to-middle dosage of glutamine in IBD patients.

One female patients with severe metastatic cancer was performed the operation of "exploratory laparotomy,primary cytoreductive surgery,partial hepatectomy,splenectomy,diaphragmatic muscle tumor resection" under the general anesthesia,and the operation time was more than 12 h.The low temperature occured due to tissue adhesion,the long operation time,massive bleeding,large area and long time exposure to internal organs and body,large infusion and application anesthetic etc.Many intervention measures were used such as preoperative warm,increasing the environmental temperature,covering for keeping warm,heating the intravenous fluids and a body cavity rinses during operation.The patients' temperature was kept in 36.8°C,and no low temperature happened.

BACKGROUNDInvasive pulmonary aspergillosis (IPA) is a severe and frequently fatal disease in patients receiving treatment with immunosuppressive agents such as cyclophosphamide. Aspergillus fumigatus (A. fumigatus) now is a leading cause of IPA. Dectin-1 and Toll-like receptor 2 (TLR2) are important pattern recognition receptors involved in immune responses to A. fumigatus in vitro. However, the expression of the two receptors during the infection of A. fumigatus in vivo is not completely understood. The effects of cyclophosphamide treatment on the expression of the receptors need to be further studied.

METHODSWe established different immune status in mice models with or without A. fumigatus infection. On days 1, 3 and 5 post inoculation, pulmonary tissues from mice of the different groups were harvested. Dectin-1 and TLR2 mRNA expression in the lungs of the mice were investigated by real-time PCR. The pulmonary fungal burden in the mice with A. fumigatus infection was also evaluated.

RESULTSIn the immunocompetent mice, three days after A. fumigatus inoculation, dectin-1 and TLR2 expression increased markedly compared with the normal control group. Cyclophosphamide inhibited the clearance of pathogens and the expression of dectin-1 with or without A. fumigatus infection in the lungs as well. There was no statistical difference in TLR2 expression between the different immune status groups.

CONCLUSIONSOur results suggest that in vivo, dectin-1 and TLR2 are activated during the experimental period which would provide a broad range of possibilities for a specific and effective inflammatory response to kill A. fumigatus. Inhibition of dectin-1 expression may be one of the mechanisms of cyclophosphamide in the development of IPA.

Animals ; Aspergillosis ; immunology ; microbiology ; Aspergillus fumigatus ; immunology ; physiology ; Cyclophosphamide ; pharmacology ; Immunosuppressive Agents ; pharmacology ; Lectins, C-Type ; Lung ; drug effects ; metabolism ; microbiology ; Male ; Membrane Proteins ; genetics ; Mice ; Mice, Inbred BALB C ; Nerve Tissue Proteins ; genetics ; Polymerase Chain Reaction ; Toll-Like Receptor 2 ; genetics

OBJECTIVETo detect the expression of B7-H1 gene in bone marrow mononuclear cells (BMMNCs) from leukemia patients and explore its clinical implications.

METHODSThe B7-H1 mRNA expression levels of BMMNCs from 74 newly diagnosed leukemia patients and 10 normal volunteers were detected by real-time quantitative PCR. At the same time, BMMNCs from 12 patients in complete remission (CR) after chemotherapy and 5 in relapse were followed up. The correlation between the clinical features of 74 de novo leukemia patients and the expression level of B7-H1 gene was analyzed.

RESULTSThe mRNA expression level of B7-H1 gene in BMMNCs from de novo leukemia patients (RQ = 0.125) was lower than that from normal control (RQ=1). When patients achieved CR the gene expression level (RQ = 69.07) was significantly higher than that before CR (P = 0.001). After relapsed, its level (RQ=4) was still higher than that before CR (P > 0.05). No clinical parameters such as gender, age, peripheral white blood count, blast cells ratio in BM, CD34 positive cells were significantly correlated with the expression level of B7-H1 except the response to therapy. The initial expression level of B7-H1 gene in non CR patients after therapy was significantly higher than that in CR patients (RQ = 26. 91, P = 0.005).

CONCLUSIONThe mRNA expression level of B7-H1 gene in newly diagnosed leukemia patients is lower than that in normal controls, and is higher in CR patients than in newly diagnosed patients. There is a correlation between the gene expression level and responsiveness to therapy.

Adult ; Antigens, CD ; metabolism ; B7-H1 Antigen ; Female ; Humans ; Leukemia ; drug therapy ; genetics ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVESTo obtain high therapeutic effect and low toxicity single-chain immunotoxin against hepatocellular carcinoma (HCC).

METHODSHuman mutant tumor necrosis factor-alpha (mTNFalpha) was linked with the 3' end of humanized single-chain Fv against HCC (hscFv25) in pGEX4T-1 vector. The anti-HCC immunotoxin was expressed in Escherichia coli and identified by western blot. The primary tumor regression trial in nude mice bearing HCC was evaluated the targeting therapeutic value of hscFv25-mTNFalpha. The tumor tissues were stained by immunohistochemical with TNFalpha antibody.

RESULTSThe expression of single-chain immunotoxin hscFv25-mTNFalpha was 12% of total bacteria proteins. The tumor regression trials of hscFv25-mTNFalpha showed 5/5 effective. It had 2/5 completely remission and 3/5 partly remission. The therapeutic result of hscFv25-mTNFalpha was better than that of mTNFalpha (F=8.70, 0.05). The HCC tissue treated by hscFv25-mTNFalpha expressed TNFalpha positive reaction. The positive granule mainly existed in HCC cytoplasm.

CONCLUSIONThe single-chain immunotoxin hscFv25-mTNFalpha has high therapeutic effect and low toxicity. It has potentialities for clinical application.

Animals ; Immunoglobulin Fragments ; therapeutic use ; Immunohistochemistry ; Immunotoxins ; therapeutic use ; Liver Neoplasms, Experimental ; therapy ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; therapeutic use

BACKGROUND: Elastic intramedullary nail is commonly used in the treatment of fractures of children, but few studies concern the elastic intramedullary nail for treating fractures in adults. OBJECTIVE: To investigate the repair effect of elastic intramedullary nail in the treatment of 22-A fracture in forearm of adults. METHODS: From January 2015 to April 2016, a total of 21 adult patients with the 22-A fracture (35 fractures) were treated with manipulative reduction and elastic intramedullary nail fixation in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The follow-up time was 12-18 months. Radiographs were taken and the guidance of the limb function training was given at regular intervals. The Andserson scoring system was used to evaluate the patients' forearm limb function. Fracture healing, elbow, wrist joint activity and forearm rotation were recorded. The satisfactory questionnaires were recorded. The patients were divided into three grades as satisfaction, general satisfaction and dissatisfaction; simultaneously, reasons were recorded. RESULTS AND CONCLUSION: (1) The Andserson scoring was satisfactory in 16 cases accounted for 76%, general satisfaction in 3 cases accounted for 14%, dissatisfaction in 2 cases accounted for 10%. (2) Wrist joint activity increased from (172±4)° before the operation to (181±3)° at the end of the follow-up. Elbow joint activity increased from (102±18)° before the operation to (124±13)° at the end of the follow-up. Forearm rotation activity increased from (84±11)° before the operation to (155±13)° at the end of the follow-up (P < 0.05). (3) In the follow-up of the 21 patients, 13 patients were satisfied with the result of surgery; 5 patients were generally satisfied; 2 patients were dissatisfied because the limited limb functions; and 1 patient was dissatisfied because of the nail irritability; the dissatisfaction rate accounted for 14%. (4) Elastic intramedullary nail can obtain affirmative effect in the treatment of adult 22-A fracture of the forearm; and clinical application should be based on the type of fracture.

To investigate the effects of stromal cell-derived factor 1 (SDF-1) and platelet factor 4 (PF4) on the homing-related function of expanded ex vivo umbilical cord blood CD34(+) cells, purified cord blood CD34(+) cells were cultured in serum-free medium containing a HGF combination of FL + SCF + TPO (FST) with either 100 ng/ml SDF-1 alone, 100 ng/ml PF4 alone, or both of these 2 cytokines. The expansion rate of CD34(+) cells, colony formation, homing-related functions including expression of homing-related adhesion molecules of expanded CD34(+) cell, adhesion activity and chemotactic function of the re-selected expanded CD34(+) cells were evaluated at different time points. The results showed that expansion rate of CD34(+) cells and expansion multiple of CFU in SDF-1 groups were higher than those in control. The expression of CD49e on the expanded CD34(+) cells was remarkable up-regulated, in contrast, expression of CXCR-4 on the expanded CD34(+) cells was remarkable down-regulated in SDF-1 groups. The expression of CD49e, CD54 and CXCR-4 on the expanded CD34(+) cells were remarkably up-regulated in the PF4 groups. In all the SDF-1 group, PF4 group and SDF-1 plus PF4 group, the ability of expanded CD34(+) cells adhering to fibronectin layer were higher than those in the control on day 10. Spontaneous migration rate of expanded CD34(+) cells in SDF-1 groups were higher than those in control, while SDF-1-induced migration rate were lower than those in control on day 10. SDF-1-induced migration rate in PF4 groups were higher than those in control on day 10. Spontaneous and SDF-1-induced migration rate of expanded CD34(+) cells in the SDF-1 plus PF4 groups were higher than those in control on day 10. It is concluded that, SDF-1 and PF4 can up-regulate expression of adhesion molecules on expanded CD34(+) cells, and retain the adherent and migration ability of expanded CD34(+) cells, which is helpful for the homing of expanded CD34(+) cells. In short, SDF-1 and PF4 are helpful for the homing-related function of the expanded UCB HSPC.
Antigens, CD34 ; blood ; immunology ; Cell Adhesion ; drug effects ; Cells, Cultured ; Chemokine CXCL12 ; Chemokines, CXC ; pharmacology ; Chemotaxis ; immunology ; physiology ; Culture Media, Serum-Free ; Fetal Blood ; cytology ; immunology ; Hematopoietic Stem Cells ; cytology ; drug effects ; Humans ; Platelet Factor 4 ; pharmacology

To compare the expansion efficiency and function of dendritic cells derived from CB-CD34+ cells and MPB-CD34+ cells by using two-step culture method, enriched CB-CD34+ cells or MPB-CD34+ cells with immunoadsorption were primarily cultured in the presence of FL, SCF, TPO, GM-CSF for 10 days, and then further cultured with a combination of GM-CSF, IL-4, TNF-alpha, CD40Ab and PGE2 to induce DC. The DC phenotypes were detected by flow cytometry, the expansion efficiency and cell function were evaluated by mix-lymphocyte reaction (MLR), IL-12 level was detected by using ELISA and the chemotactic function mediated by secondary lymphoid tissue chemokine (SLC) was determined with Transwell plate. The results indicated that after 10 days of expansion, there were no significant difference in the percentage of CD14+CD1a- cells between CB and MPB [(40.48 +/- 16.85)% vs (28.07 +/- 23.19)%, P > 0.05], but the expansion of total cells in CB was higher than that in MPB (388.88 +/- 84.63-fold vs 79.67 +/- 10.32-fold, P < 0.01), so the yield of CD14+CD1a- cells from CB was significantly higher than that from MPB too (189.42 +/- 25.02-fold vs 28.74 +/- 23.27-fold, P < 0.01). The percentage of CD83+ DCs cultured with CD40Ab/PGE2 derived from CB were higher than those cultured with TNF-alpha derived from MPB respectively [(34.52 +/- 11.22)% vs (3.70 +/- 2.27)% and (36.69 +/- 13.36)% vs (7.34 +/- 3.364)% respectively, P < 0.01]. In the same circumstance, the yield of CD83+ DCs derived from CB was much more than that from MPB (198.72 +/- 117.53 times vs 33.95 +/- 6.19 times, P < 0.01). There were no difference in stimulating capacity, IL-12 secretion and migration capacity between DCs derived from CB and MPB. It is concluded that DCs induced from CB-CD34+ cells by two-step culture possess similar functions with that from MPB-CD34+ cells, but the yield of DCs from CB CD34+ cells is much more than that from MPB CD34+ cells.
Antigens, CD34 ; analysis ; Cell Culture Techniques ; methods ; Cell Proliferation ; Cell Separation ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; Fetal Blood ; cytology ; Hematopoietic Stem Cell Mobilization ; Humans