Antineoplastic agents-induced pulmonary toxicity is one of important reasons causing respiratory failure,which clinical manifestations are pulmonary inflammation,allergic reaction,vascular permeability reaction and pulmonary vascular disease.All of these may be caused by drug toxicity,immune response and increased capillary permeability and so on.Because of the nonspecific performance,it is important to exclude the other lung diseases.Once the diagnosis is clear,the antineoplastic gents should be immediately stopped and the patients should be timely administered high-dose eorticosteroid therapy.How to reduce the pulmonary toxicity induced by antineoplastic agents is becoming one of the future focuses about antineoplastic agents research.

Objective To synthesize 6?-butylaminocholestan-3?,5?-diol,a new analogue of anti-tumoral dendrogenin with a new method.Methods 6?-butylaminocholestan-3?,5?-diol was synthesized in 5 steps using cholesterol as the starting material,3?,5?-dihydroxyl-cholestan-6-one as the key intermediate and imidation-reduction of one-pot 2 steps as the key steps.Results The target compound was synthesized in a total yield of 62% and its structure were consistent with MS (476),HRMS (476.446 5),[?]25D(-57.0?),IR (3387),1HNMR [2.67～2.61 (1H,m,6?-H)],13CNMR spectrum and elemental analyses.Conclusion Our synthetic route to 6?-butylaminocholestan-3?,5?-diol is characterized by easily available and cheap starting material,high total yield and easy industrialization.

OBJECTIVE： To evaluate the clinical therapeutic effect of L-glutamine granules on intestinal damage of severe burn patients and the safty of the drug.METHODS： Thirty-nine severe burn patients were randomly divided into two groups： control group（C group， nineteen patients） and L-glutamine treatment group（GLN group， twenty patients） .GLN group patients were given L-glutamine in a dose of 30g per day for 7 days， and C group patients were given the same dosage of placebo for 7 days.The plasma L-glutamine concentration， the degree of intestinal mucosa damage， blood biochemistry and complication were observed and wound healing rate of burn area was determined， then the length of hospital stay was recorded.RESULTS： After 7 days of taking L-glutamine orally， plasma L-glutamine concentration in GLN group was significant higher than that in C group（P<）. The degree of intestine damage and intestinal mucosal permeability in GLN group were lower than those in C group. In addition, the wound healing rate was faster and the length of hospital stay was shorter in GLN group than those in C group. CONCLUSION: Administration of L-glutamine could abate the degree of intestine damage obviously, lessen intestinal mucosal permeability, ameliorate wound healing rate and reduce the length of hospital stay.

Objective To investigate the role of Ras-related C3 botulinum toxin substrate 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (Rac 1/MAPK/ERK) signal pathway in rats with ventilator induced lung injury (VILI) and its mechanism.Methods Thirty Sprague-Dawley (SD) rats were randomly divided into spontaneous respiration group,normal tidal volume (VT) group and high VT group with 10 rats in each group.The rats in spontaneous respiration group were kept their spontaneous breathing.The rats in normal VT group and high VT group were performed tracheal intubation after tracheostomy,and underwent mechanical ventilation on bilateral lungs with 6 mL/kg and 40 mL/kg VT respectively with maintenance anesthesia.After 4-hour ventilation,heart blood,bronchoalveolar lavage fluid (BALF) and lung tissues were harvested.The levels of interleukins (IL-1β,IL-6),tumor necrosis factor-α (TNF-α),myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) in serum and BALF were determined by enzyme linked immunosorbent assay (ELISA).Lung wet/dry radio (W/D) was determined.The lung tissues were stained with hematoxylin and eosin (HE),and pathological changes were observed,and pathological scores were evaluated.The ultra structure changes in type Ⅱ alveolar epithelial cells (AEC Ⅱ)were observed with transmission electron microscope.The positive expressions of phosphorylation of extracellular signal-regulated kinase (p-ERK) were determined by immunohistochemistry,and those of Racl and F-actin were determined by immunofluorescence.The mRNA expressions of ERK and Rac1 were determined by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR),and protein expressions of Rac-1,p-ERK and F-actin were determined by Western Blot.Results ① Compared with spontaneous breathing group,lung W/D in both mechanical ventilation groups was significantly increased,with more significant increase in the high VT group (6.64 ± 0.88 vs.1.79 ± 0.36,P ＜ 0.01).② There was no obvious pathological changes in the lung tissue and AEC Ⅱ of the spontaneously breathing group.In the normal VT group,there was slight edema and infiltration of inflammatory cells;AEC Ⅱ had less lamellar bodies and uniform distribution of the villi of the alveolar epithelium.In the high VT group,the edema of the lung tissue,the widening of the pulmonary septum,the alveolus congestion,the infiltration of inflammatory cells,and alveolar structure disorder were found;and AEC Ⅱ was irregular,the number of lamellar bodies in the plastids was decreased and was unevenly distributed.The pulmonary histopathological score in the high VT group was significantly higher than that in the spontaneous breathing group and the normal VT group (12.00 ± 2.00 vs.6.00 ± 1.51,8.50 ± 0.53,both P ＜ 0.01).③ Compared with spontaneous breathing group,IL-1β,IL-6,TNF-α,MPO,and MIP-2in serum and BALF in both mechanical ventilation groups were significantly increased,with more siguificant increase in the high VT group [serum IL-1 β (ng/L):104.2 ± 15.1 vs.20.3 ± 8.3,IL-6 (ng/L):46.6 ± 11.5 vs.22.7 ± 7.5,TNF-α (ng/L):39.4±6.5 vs.5.4± 1.9,MPO (ng/L):0.66±0.24 vs.0.06±0.03,MIP-2 (ng/L):109.2±25.8 vs.22.8±8.4;BALF IL-1 β (ng/L):121.5 ± 25.6 vs.24.0 ± 7.5,IL-6 (ng/L):136.7 ± 32.7 vs.31.4 ± 10.5,TNF-α (ng/L):98.0 ± 14.8vs.10.1 ±2.6,MPO (ng/L):0.80±0.31 vs.0.08±0.04,MIP-2 (ng/L):144.4±28.9 vs.41.2±20.7;all P ＜ 0.01].④ There were only a few p-ERK,Rac1 and F-actin positive expressions in the spontaneous breathing group.The positive expressions in normal VT group were increased.In high VT group,the positive expression of p-ERK was significantly increased;Rac1 and F-actin were mainly distributed in the cell membrane and cytoplasm respectively,the positive expressions were further enhanced.⑤ The gene expressions of ERK and Rac1,and protein expressions of p-ERK,Rac1 and F-actin in the high VT group were significantly higher than those in the spontaneous breathing group and normal VT group [ERK mRNA (2-△△Ct):8.23±2.83 vs.1,3.02± 1.38,p-ERK protein (gray value):1.15±0.36 vs.0.61 ±0.23,0.88±0.22;Rac1 mRNA (2-△△Ct):4.45 ±2.26 vs.1,1.22±0.39,Rac1 protein (gray value):0.91 ±0.16 vs.0.48±0.11,0.55 ± 0.10;F-actin protein (gray value):0.70± 0.09 vs.0.49 ± 0.08,0.55 ± 0.04;all P ＜ 0.01].Conclusion F-actin expression in lung tissue was up-regulated in rats with VILI,which resulted in reconstruction of AEC Ⅱ cyto-skeleton,and variation of cell membrane permeability through Rac 1 /MAPK/ERK sigualing pathway during VILI.

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT). 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft-versus host disease (aGVHD) was prevented by cyclosporin A and short-term MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 x 10(8)/kg and that of the CD34+ cells was 7.8 x 10(6)/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got II degrees-IV degrees aGVHI) and the incidence was 17.5%. Fourteen patients got cGVHD and the incidence was 53.8% in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5% and 2 patients relapsed (5.0%). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.
China/epidemiology ; Cyclosporine/*therapeutic use ; Follow-Up Studies ; Graft vs Host Disease/*prevention & control ; Leukemia/*therapy ; Leukemia, Lymphoid/therapy ; Leukemia, Myeloid, Acute/therapy ; *Peripheral Blood Stem Cell Transplantation/adverse effects ; Sepsis/epidemiology ; Sepsis/etiology

OBJECTIVETo investigate the effect of rapamycin, an mTOR inhibitor, on learning and memory ability of mice with pilocarpine (PILO)-induced seizure.

METHODSOne hundred and sixty male adult ICR mice were randomly grouped as vehicle control (n=20), rapamycin control (n=20), PILO model (n=40), rapamycin pre-treatment (n=40) and rapamycin post-treatment (n=40). PILO model and rapamycin treatment groups were injected with PILO to induce temporal lobe seizure. Rapamycin was administrated for 3 days before or after seizure. Morris water maze, Y maze and open field were used for the assessment of learning and memory, and FJB and Timm staining were conducted to detect the neuronal cell death and mossy fiber sprouting, respectively.

RESULTSNo significant cell death was observed in the mice with PILO-induced seizure. The learning and memory were impaired in mice 7 to 10 days after PILO-induced seizure, which was evident by prolongation of avoiding latency (P<0.05), decrease in number of correct reaction (P<0.01) and number of crossing (P<0.05). Treatment with rapamycin both pre-and post- PILO injection reversed seizure-induced cognitive impairment. In addition, rapamycin inhibited the mossy fiber sprouting after seizure (P<0.001).

CONCLUSIONRapamycin improves learning and memory ability in ICR mice after PILO-induced seizure, and its mechanism needs to be further studied.

Animals ; Cell Death ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred ICR ; Neurons ; drug effects ; pathology ; Pilocarpine ; toxicity ; Sirolimus ; pharmacology

OBJECTIVETo observe the effect of different nutritional routes of giving nutrition on the intestinal mucus barrier in severely scalded rats.

METHODSWistar rats inflicted with 30% TBSA III degree scalding on the back were employed as the model and were randomly divided into 3 groups, i.e. control (C), parenteral nutrition (PN) and enteral nutrition (EN) groups. The rats in PN and EN groups were supplied with equal amount of nitrogen and calories and with equal volume of nutrition solution. The dynamic changes in the thickness of intestinal mucus layer and the contents of protein, hexose and acetylneuraminate in the mucus were examined.

RESULTSWhen compared with those in C group, the intestinal mucus layer became thinner and the contents of protein, hexose and acetylneuraminate in the mucus in both PN and EN groups decreased evidently after scalding. When compared between two nutritional groups, the thickness of intestinal mucus layer and the contents of the hexose and acetylneuraminate in the mucus in EN were much thicker and higher than those in PN group, while the mucus protein content exhibited no obvious difference between PN and EN groups.

CONCLUSIONIt was suggested that intestinal goblet cell synthesized and secreted less mucus after scalding in rats resulting in thinning of intestinal mucus layer and the change in mucus components. When compared with those in PN group, less injury to the intestinal goblet cells occurred and the intestinal mucus synthesis was less affected in EN group, and the components of intestinal mucus were maintained stable.

Animals ; Burns ; metabolism ; Enteral Nutrition ; Female ; Hexoses ; metabolism ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Parenteral Nutrition ; Proteins ; metabolism ; Rats ; Rats, Wistar ; Sialic Acids ; metabolism ; Time Factors

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Objective To investigate the value of quantitative analysis of the left ventricular longitudinal strain in patients with hypertrophic cardiomyopathy (HCM) and with normal left ventricular ejection fraction (LVEF) by using two-dimensional speckle tracking imaging.Methods Twenty-eight HCM patients with normal LVEF (all of the cases were non obstructive HCM),who were diagnosed by clinical and ultrasound echocardiography between January 1,2015 and January 1,2016 in the First Affiliated Hospital of Dalian Medical University,served as the experimental group.And twenty healthy volunteers served as the healthy control group.The peak longitudinal strain (LPS) of the left ventricle and the systolic peak of the left ventricle were calculated by the STE technique.The indexes such as the transmural gradient (△ LS=LPSEndo-LPSEpi)and the transmural gradient percentage (△ LS％=△ LS/LPSEndo) were calculated.The Peak systolic longitudinal strain of endocardium (LPSEndo),the peak systolic longitudinal strain of mid-cardium (LPSMid),the peak systolic longitudinal strain of epicardium (LPSEpi),the peak systolic longitudinal strain of basal segment (LPSb),the peak systolic longitudinal strain of middle segment (LPSm),the peak systolic longitudinal strain of apical segment (LPSa),the global peak systolic longitudinal strain (GLPS) and other left ventricular myocardial strain,such as △ LS,△ LS％,in both the HCM group and the healthy control group,were analyzed by using independent samples t test comparison.For each layer of the left ventricle and the overall myocardial longitudinal strain,two independent sample t test was used for comparison between groups,and LSD-t test was used for intra-group comparison.Results (1) There was a gradient of LPS among the three layers and the three segments in both of the two groups:LPSEndo and LPSMid [(18.36±4.97)％ vs (13.80±4.23)％,(26.41±2.93)％ vs (22.19±2.49)％],the difference was statistically significant (t=5.550,8.529,P ＜ 0.05);LPSEndo and LPSEpi [(18.36±4.97) ％ vs (11.91 ±3.63)％,(26.41±2.93)％ vs (19.43±2.20)％],the difference was statistically significant (t=5.550,8.529,P ＜ 0.05);There was significant difference between LPSMid and LPSEpi in the healthy control group [(22.19 ± 2.49)％ vs (19.43 ± 2.20)％,t=3.709,P ＜ 0.05)],that was,LPSEndo ＞ LPSMid ＞ LPSEpi.LPSa and LPSm,the difference was statistically significant (t=4.029,6.839,P ＜ 0.05);LPSa and LPSb,the difference was statistically significant (t=5.304,9.887,P ＜ 0.05);There was significant difference between LPSm and LPSb in the healthy control group (t=4.170,P ＜ 0.05);that was,LPSa ＞ LPSm ＞ LPSb.In the HCM group,LPS in the 3 layers,3 segments,and the whole left ventricular wall were lower than that of the the healthy control group,the differences were statistically significant [GLPS:(14.63± 3.75)％ vs (22.68±2.51)％,t=-8.347;LPSEndo to LPSEpi:t=-6.477,-7.909,-8.242;LPSa to LPSb:t=-6.647,-8.790,-7.267;all P ＜ 0.05).(2) Compared with the healthy control group,both the segmental gradient and global transmural gradient in the HCM group were found reduced,but the difference had no statistical significance (all P ＞ 0.05).(3) The transmural gradient percentage both in the healthy control group and the HCM group were reduced from the apical segment to the basal segment,the difference were statistically significant (HCM group:t=9.985,5.969;healthy control group:t=17.513,7.043;all P ＜ 0.05).Compared with the healthy control group,the △ LS％a and the △ LS％m of HCM group were significantly higher [(58.86± 11.32)％ vs (43.70±4.73)％,(28.43± 11.48)％ vs (20.30± 3.66)％],and the difference was statistically significant (t=5.634,3.049,all P ＜ 0.05).Conclusions (1) Using 2D-STI could accurately determine the regional or the global left ventricular systolic function in patients with HCM.(2) The transmural gradient percentage can be more sensitive to reflect the change of the transmural gradient,and more research needed to explore its value for clinical application.

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT), 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft versus host disease (aGVHD) was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 × 108/kg and that of the CD34+ cells was 7.8 × 106/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ε° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months.Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5 % and 2 patients relapsed (5.0 %). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.