Objective: To investigate the efficacy and safety of high-dose recombinant human interleukin-2 (rhIL-2) in treatment of patients with advanced melanoma. Methods: Twenty Chinese patients with advanced melanoma were planned to be enrolled to receive high-dose rhIL-2 treatment. The overall response rare (ORR), progression-free survival (PFS), overall survival (OS) and incidence of toxicity were evaluated. Results: Fourteen patients were enrolled, of them twelve could be evaluated. One patient achieved partial response (PR), and the maintaining duration of response was 43.0 months; three patients achieved stable disease (SD); 8 patients achieved progressive disease (PD). The median PFS was 56.0±7.6 d, and the median OS was 11.0±2.6 months. The incidence rate of grade III-IV toxicity was 40.3%, mainly manifested as gastrointestinal reaction, fever and cardiovascular reaction. Conclusion: The efficacy of high-dose rhIL-2 for Chinese patients with advanced melanoma is not as good as those previously reported in studies abroad, with high incidence rate of adverse effects. The patients can get long response duration as rhIL-2 worked. It is necessary to perform further studies on how to make choice of administration dose and select potential patients who will benefit from the treatment. Copyright© 2011 by TUMOR.

Objective To study the molecular mechanism of different sensitivities to apoptosis induced by low concentration of As2O3 in PML-RARα negative HL-60 cells and PML-RARα positive NB4 cells. Meth-ods NB4 and HL-60 cells were cultured with As2O3 for 1 to 4 days; cell proliferation were detected by MTT method; the apoptosis was detected by flow cytometry,Bcl-2,Bax and Fas mRNA were determined by RT-PCR. Results The proliferation of NB4 cells was inhibited obviously by As2O3(1.0 μmol/L)with the induction of apoptosis( P <0.05) ,which was accompanied by the down-regulation of Bcl-2 mRNA expression( P <0.05)and the ratio of Bcl-2/Bax(P <0.05), but there was no obvious variation of Bax and Fas expression( P >0.05). Inhibition of proliferation and apoptosis were not obvious in PML-RARα negative HL-60 cells induced by low concentration As2O3 ( P >0.05), and there was no obvious variation of Bcl-2, Bax, Fas mRNA expres-sion or Bcl/Bax ratio( P >0.05). Conclusion The ratio of Bcl-2/Bax is contributed to the different sensitiv-ities of PML-RARα negative HL-60 cells and positive NB4 cells induced by low concentration of As2O3.

Objective To observe the clinical features of atrial fibrillation (AF) patients, and to explore the correlation between the routine detection index and the new-onset AF and to find out risk factors for new AF in critically ill patients. Methods A prospective observational study was conducted. The patients with AF admitted to intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from March 2016 to June 2017 were enrolled. The patients were divided into new-onset AF group and past-existed AF group according to their past history of AF (including persistent AF, paroxysmal AF or permanent AF). In addition, patients in ICU without history of AF and new-onset AF were selected as the control group (no AF group). The general epidemiological characteristics of patients in three groups, and the blood biochemical, coagulation and other related indicators at the time of AF occurred (new-onset AF group) or 48 hours after ICU admission (AF group and no AF group) were analyzed; the difference of laboratory indexes between patients in new-onset AF group with AF within 48 hours before occurred and patients in no AF group within 48 hours after admission to ICU was compared. The relationship between each index and new-onset AF were analyzed. Pearson or Spearman rank correlation was used for analysis. Risk factors of new-onset AF were analyzed by Logistic regression analysis. Results 1 673 patients were admitted to ICU, including 179 cases of AF (10.70%), and 106 males and 73 females, with an average age of (71.73±23.22) years. There was 75 new-onset AF (morbidity 4.48%), and had a 28-day mortality of 45.33% (34/75). There were differences in age, previous heart disease and heart failure (HF) among new-onset AF group (n = 75), past-existed AF group (n = 104) and no AF group (n = 75). Compared with other two groups, renal insufficiency rates, troponin, serum sodium, calcium and procalcitonin levels were higher, mechanical ventilation time and the length of ICU stay were significantly prolonged, ICU and hospitalization costs were higher in new-onset AF group. Compared with no AF group, new-onset AF patients with the higher percentage of septic shock, the accumulation of vascular contraction drugs within 24 hours after AF usage were higher, and used more anti-arrhythmic drugs, has higher brain natriuretic peptide (pro-BNP), serum creatinine, blood lactic acid levels, and lower albumin, oxygenation index, and serum potassium levels, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score and 28-day mortality were higher. Correlation analysis showed that age, APACHE Ⅱ score, septic shock, HF, cardiovascular disease, renal insufficiency were positively correlated with new-onset AF (r values were 0.393, 0.270, 0.386, 0.251, 0.194, 0.170;P values were 0.000, 0.001, 0.000, 0.002, 0.017, 0.037, respectively). The age [odds ratio (OR) = 0.962, P = 0.046], basic oxygenation index (OR = 1.005, P = 0.028) and serum potassium levels (OR = 1.638, P = 0.022) were the risk factors for new-onset AF. Conclusions Critical patients with a high incidence of AF, new-onset AF significantly prolong the length of ICU stay; age, APACHE Ⅱ score, septic shock, cardiovascular disease, and renal insufficiency are related to new-onset AF; age, basic oxygenation index and serum potassium levels are risk factors for new-onset AF.

BACKGROUNDp53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4(+) T lymphocytes from patients with active rheumatoid arthritis (RA).

METHODSHuman FLS were transfected with p53 siRNA and cocultured with CD4(+) T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-γ, IL-17, IL-4 and CD25 as well as mRNAs of IFN-γ, retinoic acid-related orphan receptor (ROR)-γt, IL-17 and Foxp3 in cocultured CD4(+) T lymphocytes were also measured.

RESULTSIL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-γ by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes.

CONCLUSIONp53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA.

Arthritis, Rheumatoid ; genetics ; immunology ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Forkhead Transcription Factors ; genetics ; metabolism ; Humans ; Interleukin-6 ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Synovial Membrane ; cytology ; Tumor Suppressor Protein p53 ; genetics ; metabolism

AIMGenetic diversity, relationship and molecular authentication of total 8 wild populations of Dendrobium officinale were investigated using RAPD markers.

METHODS10 random decamer primers were screened for Random Amplified Polymophic DNA (RAPD) fragments. A DNA molecular dendrogram was established based on cluster analysis by UPGMA (unweighted pair-group method with arithmetic average), and the relationship of the wild populations were analyzed, and all the wild populations were authenticated.

RESULTSA total of 439 loci with an average of 43.9 loci per primer and 54.9 loci per population were amplified from 8 wild populations by 10 effective primers. In the total 104 amplified bands, 95 were polymorphic, corresponding to 91.35% genetic polymorphism. The genetic distances were 0. 590 to 0. 727, with an average of 0. 686.

CONCLUSIONDistinct genetic differences and extensive genetic diversity were presented among the wild populations. RAPD markers were an informative and useful tool for the genetic diversity, evaluation and authentication of wild populations of Dendrobium officinale. Primer S412 could be used to authenticate 8 wild populations completely.

China ; Cluster Analysis ; DNA Fingerprinting ; DNA Primers ; DNA, Plant ; genetics ; Dendrobium ; genetics ; Ecosystem ; Genetic Markers ; Genetic Variation ; Phylogeny ; Plants, Medicinal ; genetics ; Random Amplified Polymorphic DNA Technique

OBJECTIVETo study the protective effect of intensive insulin treatment on the myocardium of severely scalded rats, and to primarily explore its mechanism.

METHODSEighteen SD rats were divided into three groups, with 6 rats in each group. The rats in burn and intensive insulin group were inflicted with 30% TBSA full-thickness injury on the back. Isotonic saline containing 0.12 U/ml insulin solution, and 100 g/L glucose solution were infused into the rats in the intensive insulin group to keep plasma glucose at the level of 4.0 - 6.6 mmol/L (the total fluid amount was 2 ml x kg(-1) x 8h(-1)). In sham burn group,fluid was given according to physiological demand. The same amount of isotonic saline was infused into the rats in burn group. The venous blood was obtained for the detection of plasma glucose contents, and the left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were recorded via aortic ventricle cannula before scald and at 1, 2, 3, 4, 5, 6 post-scald hours (PSH). The tissue of the left ventricle was harvested at 6 PSH for the detection of troponin T expression in myocardiocytes.

RESULTSPlasma glucose level was increased to (7.6 +/- 1.7) mmol/L - (8.4 +/- 4.7) mmol/L in burn group during 1-6 PSH, which was significantly higher than that in intensive insulin group (4.5 +/- 0.9) mmol/L - (5.2 +/- 1.3) mmol/L, P < 0.01). Compared with the intensive insulin group, LVSP was markedly decreased in the burn group (60 +/- 11 mm Hg vs 72 +/- 8 mm Hg, P < 0.05) at 1 PSH,whereas LVEDP was increased significantly (21.3 +/- 11.3 mmHg vs 11.7 +/- 5.2 mmHg, P < 0.05). Intensive insulin treatment could significantly inhibit the loss of troponin T protein in myofilaments of myocardium.

CONCLUSIONIntensive insulin treatment possesses a protective effect on myocardia function after severe burns, and it may be related to its preventive effect on the loss of contractile protein in cardiocytes.

Animals ; Blood Glucose ; metabolism ; Burns ; drug therapy ; metabolism ; Insulin ; administration & dosage ; therapeutic use ; Male ; Myocardial Contraction ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Troponin T ; metabolism

OBJECTIVETo determine whether U50488H, a selective agonist of kappa-opioid receptor, could induce biphasic (early and late) cardioprotection against myocardial ischemia/reperfusion injury and to explore the underlying mechanisms.

METHODSIsolated perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion and the cardiac function was evaluated.

RESULTLeft ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) and maximal velocity of contraction and relaxation (+/-dP/dtmax) were improved when U50488H was administered 1 or 24 h before ischemia (P<0.05). Myocardial infarct size, activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent were lower in the U50488H pretreatment group than those in the control group. Administration of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib abolished the late phase of cardioprotection produced by administration of U50488H 24 h before ischemia. Activities of CK and LDH in the coronary effluent were higher in U50488H and celecoxib co-pretreatment group than those in U50488H group. However, administration of celecoxib did not block the early phase of cardioprotection by 1 h treatment of U50488H before ischemia.

CONCLUSIONThe late (but not the early) phase of cardioprotection induced by kappa-opioid receptor agonist might be mediated by COX-2.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Creatine Kinase ; metabolism ; Cyclooxygenase 2 ; physiology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; L-Lactate Dehydrogenase ; metabolism ; Male ; Myocardial Infarction ; enzymology ; pathology ; Myocardial Reperfusion Injury ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

Objective To explore the influence factors of help-seeking behavior in people with subjective memory complaints (SMCs).Methods A total of 305 eligible SMCs people were recruited and investigated with illness perception questionnaire-memory (IPQ-M),GDS-15,Mini-mental State Examination (MMSE),auditory verbal learning test(AVLT).Subjects were comprised of two groups:help-seeking group(n=44) and non-help-seeking group(n=261).Results The ratio of SMCs people for help-seeking was very low,only accounted for 14.4％.The ratio for going to hospital to see a specialist memory clinic accounted for only 2.0％.Logistic regression analysis showed 6 related factors were prime motivators for help-seeking behavior,which were symptom (OR=1.455),treatment control (OR=2.456),emotional representation (OR=2.268),accepting dementia education (OR=1.576),lacking of blood supply to the brain(OR=1.115),not using brain(OR=2.079).Three causal attributions were obstructive factors for help-seeking behavior,which were loneliness (OR=0.253),aging (OR=0.450),and chance or bad luck (OR=0.374).Conclusion Illness perception-memory in subjects with SMCs had some prediction for help-seeking behavior.Community nurses should attach importance to illness perception-memory of SMCs people and help them promote help-seeking,so as to facilitate earlv screening,identification and prevention of dementia.

Objective To study on the anti-fatigue and hypoxia tolerance function of Jasmine leaves' water extract in mice.Methods Forty-eight normal male mice were averagely selected and divided into four groups by weight:blank control group,low concentration experimental group,medium concentration experimental group and high concentration experimental group.Jasmine leaves' water extract of different concentrations (0,200,400,600 mg· mL-1 respectively for the four groups) was given into the mice's stomach for a continuous 16 days,each mice was given 10 mL · kg-1 a day.Burdened swimming test and hypoxia tolerance test were conducted in the mice to determine their swimming time and death time.The liver weight coefficient was calculated.Results The burdened swimming time:Compared with blank control group 9.27 min,that were 9.41,15.42,10.63 min in low,medium,high concentrations experimental groups respectively while medium experimental group had significantly (P ＜ 0.05).The hypoxia tolerance time:Compared with blank control group (47.56 ± 5.61)min,that were (56.24 ± 10.99),(47.20 ± 4.51),(53.44 ± 7.56) min in low,medium,high concentrations experimental groups respectively while low experimental group had significantly (P ＜ 0.01).The liver weight coefficient:Compared with blank control group (4.84 ± 0.29) × 10-2,that were (5.20 ± 0.72) × 10-2,(5.43 ±0.39) × 10-2,(5.42 ± 0.57) × 10-2 in low,medium,high concentrations experimental groups respectively while medium,high experimental groups had significantly(all P ＜ 0.01).Conclusion Jasmine leaves' water extract is proved to have anti-fatigue and hypoxia tolerance function in mice.

Objective:To investigate the role and molecular mechanism of Na+/Ca2+ exchanger 1 (NCX1) in the invasion and proliferation of hepatocellular carcinoma (HCC),and to provide new therapeutic targets for the clinical diagnosis and treatment of hepatocellular carcinoma.Methods:Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect NCX1 mRNA and protein expression in different HCC cell lines.Lentiviral vectors pGC-SIL-GFP-shRNA-NCX1 and pGC-FU-GFP-NCX1 were constructed and transfected into hepatoma cells.Cell migration and invasion experiments were used to observe the effect of NCX1 on the migration and invasion of HCC cells;cell proliferation assay was used to observe the effect of NCX1 on the proliferation of hepatoma cells;Western blotting and ELISA were used to detect the expressions of NCX1-related proteins.Results:The expression of NCX1 in high metastatic potential HCC cell lines (MHCC97H,HCCLM3) was higher than that of low metastatic potential HCC cell lines (HepG2,Huh7,SMMC-7721),and the difference was statistically significant (P＜0.05).After transfection of NCX1,the invasion and proliferation ability of HCC cells increased significantly (P＜0.05);the secretion of cytokines (TGF-β1,IL-6 and TNF-α) increased significantly (P＜0.05);the expressions of epithelial-mesenchymal transition (EMT) related proteins in HCC cells were significantly increased (P＜0.05).Conclusions:NCX1 can promote the growth,invasion and metastasis of hepatocellular carcinoma by increasing the expressions of EMT-related proteins in HCC cells,and it is a potential target for the diagnosis and treatment of liver cancer.