Analysis of Ki67 Protein Expression and Clinicopathological Features in Patients with Peritoneal Mesothelioma.

Background: At present, there are many treatments for peritoneal mesothelioma, but the treatment of peritoneal mesothelioma is still facing great challenges. Distant metastasis is the main cause of poor prognosis and death of patients with peritoneal mesothelioma. Ki67 is a cell proliferation marker. In recent years, it has been found to be used as a molecular marker for the diagnosis, treatment and prognosis of different tumor cells. Ki67 has been shown to play a crucial role in the occurrence and development of a variety of cancers. However, the clinical significance and biological function of Ki67 in peritoneal mesothelioma remain poorly understood. Purpose: To clarify the expression of Ki67 in peritoneal mesothelioma (PC), and to explore the relationship between the expression level of Ki67 and the clinicopathological parameters and prognosis of patients with PC, and to explore the potential of Ki67 as a therapeutic target and prognostic biomarker for PC. Methods: TIMER database was used to compare the expression levels of Ki67 mRNA and protein in mesothelioma tissues and adjacent tissues. The relationship between the expression level of Ki67 in mesothelioma and clinicopathological characteristics, and the relationship between the expression level of Ki67 and the level of immune infiltration in mesothelioma were analyzed. The prognostic value of Ki67 in mesothelioma patients was predicted, and the overall survival curve was drawn according to the follow-up data. LinkedOmics database and GSEA were used to perform co-expression analysis and enrichment analysis of Ki67, respectively. Results: Bioinformatics analysis showed that Ki67 was highly expressed in peritoneal mesothelioma (P < .01). Immunohistochemistry showed that the positive rate of Ki67 in peritoneal mesothelioma was high, and the number of Ki67 positive cases was 62.0% (31/50 cases). Univariate analysis showed that TNM stage (P = .007), asbestos (P < .001), chemotherapy (P < .001), and Ki67 expression level (P = .029) were associated with prognosis. Multivariate analysis showed that Ki67 expression level (P = .039) and TNM stage (P = .029) were independent risk factors for the prognosis of peritoneal mesothelioma. Peritoneal mesothelioma patients with high Ki67 expression have poor OS. In addition, Ki67 is also associated with the immune infiltration of mesothelioma. Conclusion: Ki67 is highly expressed in peritoneal mesothelioma. Ki67 protein plays an important role in the development of peritoneal mesothelioma and is one of the important factors to evaluate the prognosis of patients with peritoneal mesothelioma.

Effect of novel botanical synergist on the effectiveness and residue behavior of prothioconazole in wheat field.

Fusarium head blight (FHB) is a critical fungal disease causes serious grain yield losses and mycotoxin contaminations. Currently, utilization of chemical fungicides is the main control method which has led to serious resistance. Development of novel synergist is an important strategy to reduce the usage of chemical fungicides and postpone the development of resistance, while natural components are interesting resources. In this study, the synergistic effect of Taxodium 'zhongshansha' essential oil (TZEO) was determined and the best synergistic ratio (SR) of 3.96 in laboratory which was observed when the weight ratio of TZEO and prothioconazole was 1 : 1 with the corresponding EC50 (half maximal effective concentration) value of Fusarium graminearum was 0.280 mg L-1. Subsequently, an increase of 6.31% on the control effect to FHB index in field test was observed when compared to the treatment with prothioconazole alone, though there was no significant difference between these treatments. Furthermore, we established an effective method to detect the mycotoxin contaminations in wheat grain with the limits of quantifications (LOQs) value of 5 µg kg-1 (DON, ZEN, 3-DON, and 15-DON) and 1 µg kg-1 (OTA) and the contents were less to the maximum residue limit (MRL) values. It was also shown that the application of 20% TZEO EW led to a 20% reduction in the use of prothioconazole, which was calculated based on the control effect values of 86.41% and 90.20% between the treatments of 30% prothioconazole OD (225 g a.i ha-1, recommend dosage) and 30% prothioconazole OD (180 g a.i ha-1) + 20% TZEO EW (225 mL ha-1), significantly. The initial residue of prothioconazole and prothioconazole-desthio was increased in the treatment with TZEO, which may play an important role in the synergistic effect on FHB. Moreover, none of the treatments posed a prothioconazole residue risk in the wheat grain and the environment. In addition, the essential oil has no any negative influence on wheat growth, which was revealed by a study of the chlorophyll content. These results provide an important botanical synergist for use with prothioconazole to control Fusarium head blight, and in-depth study to the synergistic mechanism of this oil is necessary in our future research.

[Relationship between Iron Metabolic Parameters and Platelet Counts in Blood Donors].

OBJECTIVE: To investigate the correlation of iron metabolic parameters with platelet counts in blood donors. METHODS: A total of 400 blood donors who met requirements of apheresis platelet donation were collected, and their hematological parameters were analyzed. The donors were divided into low ferritin group and normal group, the differences of hematological parameters between the two groups were compared, and the correlation of iron metabolic parameters and routine hematology parameters with platelet counts were analyzed. RESULTS: Whether male or female, low ferritin group had higher platelet counts than normal group (P < 0.01). Among the iron metabolic parameters, the platelet counts was negatively correlated with serum ferritin (SF), serum iron (SI), and transferrin saturation (TSAT) (r =-0.162, r =-0.153, r =-0.256), and positively correlated with total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) (r =0.219, r =0.294) in female blood donors. Platelet counts was also negatively correlated with SF, SI and TSAT (r =-0.188, r =-0.148, r =-0.224) and positively correlated with UIBC (r =0.220) in male blood donors. Among the routine hematology parameters, platelet counts was negatively correlated with mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and reticulocyte hemoglobin equivalent (Ret-He) in female blood donors (r =-0.236, r =-0.267, r =-0.213, r =-0.284). Platelet counts was also negatively correlated with MCH, MCHC and Ret-He in male blood donors (r =-0.184, r =-0.221, r =-0.209). CONCLUSION: In blood donors with low C-reactive protein level, the lower the iron store capacity, the lower the iron utilization, and the platelet counts tends to rise.

Identification and characterization of odorant receptors in Plutella xylostella antenna response to 2,3-dimethyl-6-(1-hydroxy)-pyrazine.

Diamondback moth (Plutella xylostella), a worldwide migratory pest that is developing strong resistance to various chemical insecticides. It has been determined that four natural pyrazines isolated from Allium tuberosum showed significant repellent activity to P. xylostella, but the molecular target still unknown. In the present study, a novel synthetic route for 2,3-dimethyl-6-(1-hydroxy)-pyrazine which has the most significant repellent activity with a purity of 90.60% was established. Simultaneously, the bioassay result declared that the repellent grade was IV at a dosage of 0.01 mg which was the same as to the published data. Transcriptomics analysis detected 1643 upregulated and 3837 downregulated genes in P. xylostella antennae following this pyrazine exposure. Then, 2142 differentially expressed genes were annotated using Gene Ontology and 2757 genes were annotated by Kyoto Encyclopedia of Genes and Genomes. Moreover, this procedure identified 84 odour perception-related genes, 58 odorant receptor (OR) genes including 57 conventional ORs and the odorant receptor co-receptor (Orco, atypical odorant receptor) gene, and 26 odorant-binding protein (OBP) genes. Based on quantitative real time PCR (RT-qPCR) and differential expression results, 9 OR genes including the Orco were cloned and characterised. In summary, this study provides important basis for the utilization of pyrazines as the main active ingredients or lead compounds to developing new botanical pesticides, which will reduce application of chemical pesticides and postpone the development of resistance.

Mechanism and Kinetics of Prothioconazole Photodegradation in Aqueous Solution.

This study investigated the effects of light source, pH value, and NO3- concentration on the photodegradation of prothioconazole in aqueous solution. The half-life (t1/2) of prothioconazole was 173.29, 21.66, and 11.18 min under xenon, ultraviolet, and high-pressure mercury lamps, respectively. At pH values of 4.0, 7.0, and 9.0 under a xenon lamp light source, the t1/2 values were 693.15, 231.05, and 99.02 min, respectively. Inorganic substance NO3- clearly promoted the photodegradation of prothioconazole, with t1/2 values of 115.53, 77.02, and 69.32 min at NO3- concentrations of 1.0, 2.0, and 5.0 mg L-1, respectively. The photodegradation products were identified as C14H15Cl2N3O, C14H16ClN3OS, C14H15Cl2N3O2S, and C14H13Cl2N3 based on calculations and the Waters compound library. Furthermore, density functional theory (DFT) calculations showed that the C-S, C-Cl, C-N, and C-O bonds of prothioconazole were the reaction sites with high absolute charge values and greater bond lengths. Finally, the photodegradation pathway of prothioconazole was concluded, and the variation in energy of the photodegradation process was attributed to the decrease in activation energy caused by light excitation. This work provides new insight into the structural modification and photochemical stability improvement of prothioconazole, which plays an important role in decreasing safety risk during application that will reduce the exposure risk in field environment.

Efficacy and Mechanism of Trimebutine Maleate Combined with Lactulose in the Treatment of Constipation-Predominant Irritable Bowel Syndrome in the Elderly.

Objective: Study on the efficacy and mechanism of trimebutine maleate combined with lactulose in the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in the elderly. Methods: From March 2019 to March 2021, 102 elderly patients with IBS-C were randomly divided into the observation group (51 cases) and the control group (51 cases). The observation group was treated with trimebutine maleate combined with lactulose, while the control group was treated with lactulose. Comparison of the clinical effects of the two groups. Comparison of vasoactive intestinal peptide (VIP) levels, neuropeptide Y (NPY) levels, and quality of life scores before and after treatment between the two groups. Documentation of adverse reactions during treatment. Results: The improvement of clinical symptoms in the observation group was significantly better than that in the control group, and the difference is statistically significant (P < 0.05). The level of VIP after treatment in the observation group was significantly lower than that in the control group and before treatment, and the differences were statistically significant (P < 0.05). The level of NPY after treatment in the observation group was significantly higher than that in the control group and before treatment, and the differences were statistically significant (P < 0.05). The scores of dietary restrictions and health worries in the control group after treatment were significantly higher than those before treatment, and the differences were statistically significant (P < 0.05). The scores of anxious, behavioral conflict, dietary restrictions, health worries, social response, and family relationship in the observation group after treatment were significantly higher than those in the control group and before treatment, and the differences were statistically significant (P < 0.05). There were no serious adverse effects in either group during the treatment period, with some patients experiencing dizziness and dry mouth, which improved after discontinuation of the drug, without special intervention. Conclusion: Trimebutine maleate combined with lactulose can improve clinical symptoms and quality of life in elderly patients with IBS-C, and its mechanism of action may be related to the regulation of the body's VIP and NPY levels.

Effects of MSCT enhanced scan image diagnosis on clinical outcome of patients after radical gastrectomy and its influence on misdiagnosis rate.

PURPOSE: To explore the effect of multi-slice spiral computed tomography (MSCT) enhanced scan image diagnosis on clinical outcome of patients after radical gastrectomy and its influence on misdiagnosis rate. METHODS: A total of 62 patients diagnosed with gastric cancer and undergoing radical gastrectomy were selected. All patients were reexamined 2-6 months after operation. Conventional CT and MSCT enhanced scan were performed for image diagnosis, and the results were compared with those of gastroscopic biopsy. Finally, the misdiagnosis rate, negative predictive value, positive predictive value, sensitivity and specificity of conventional CT and MSCT enhanced scan for postoperative recurrence were analyzed. RESULTS: According to the results of gastroscopic biopsy, there were 35 cases suspected of recurrence, and 27 cases without postoperative recurrence. The specificity and sensitivity of conventional CT and MSCT enhanced scan were 85.19% vs. 92.59%, and 65.71% vs. 92.16%, respectively. Both specificity and sensitivity of MSCT enhanced scan were higher than those of conventional CT, with statistically significant differences (p<0.05). MSCT enhanced scan had a lower misdiagnosis rate for postoperative recurrence than conventional CT (5.71% vs. 22.86%) (p<0.05). Moreover, the negative predictive value and positive predictive value of conventional CT and MSCT enhanced scan were 65.71% vs. 86.21%, and 85.19% vs. 93.94%, respectively. The results showed that MSCT enhanced scan had higher negative predictive value and positive predictive value for postoperative recurrence than conventional CT, with statistically significant differences (p<0.05). CONCLUSION: MSCT enhanced scan image diagnosis is of great significance for assessing the condition of disease, determining the recurrent foci after radical gastrectomy, and developing the subsequent therapeutic regimen.

[Analysis of Iron Stores in the Plateletpheresis Donors].

OBJECTIVE: To understand the iron stores of the plateletpheresis donors, so as to provide some new experimental data for further exploration and more perfect health examination criteria of the plateletpheresis donors. METHODS: A total of 297 plateletheresis donors conformed to standard in October 2018 were selected by the cross sectional study. The related factors affecting iron stores were analyzed; the effect of plateletpheresis times of donation on the levels of the hemoglobin(Hb) and serum ferritin(SF) as well as the iron deficency rate in the blood donors was also analyzed; the iron stores in the blood donors was evaluated. RESULTS: The SF level in plateletpheresis donors negatively correlated with annual plateletphersis times of donation（r=-0.416, P＜0.001）; The SF level decreased with the increase of annual times of donation（P＜0.05）; The iron deficiency rate in plateletpheresis donors showed the increase trend with the increase of annual times of donation. The iron deficiency rate in male and femal with 18-23 times of donation was 12.5%(8/64) and 40%(6/15) respectively. CONCLUSION: The blood center should reduce recruitment frequency and increase the testing of SF for regularly plateletpheresis donors.

Guidelines for parenteral and enteral nutrition support in geriatric patients in China.

The mortality and morbidity of geriatric patients is much higher than for younger patients, especially when critically ill. This may be attributed to a lower reserve capacity in most organs and systems, reduced ability to deal with physical stress and the presence of acute or chronic co-mobidities. Parenteral and enteral nutrition support can improve the clinical condition of the elderly patient and result in better outcomes, such as lower mortality, reduced hospital stay and reduced medical costs. There is a need to standardize nutrition screening and assessment, and the implementation of appropriate evidence based nutritional support of geriatric patients in China. The Chinese Medical Association's Group of Geriatric Nutrition Support has developed guidelines by researching the present situation in Chinese hospitals and by referring to the guidelines from both American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism (ESPEN).

Geminin interference facilitates vascular smooth muscle cell proliferation by upregulation of CDK-1.

PURPOSE: Geminin has been correlated with vascular smooth muscle cell (VSMC) proliferation, but its mechanism is unclear. We selectively silenced the geminin gene of rat VSMCs by using RNAi technology and examined how geminin regulated VSMC proliferation. METHODS: By using RNA interference in A10 cells and flow cytometry, (3)H-thymidine and 5-ethynyl-2'-deoxyuridine (EdU) measurements were used to detect VSMC proliferation. We performed a Western blot, polymerase chain reaction, and immunohistochemistry to detect the expression and location of geminin and cyclin-dependent kinase-1 (CDK1) in VSMCs. RESULTS: Silencing geminin significantly increased (3)H-thymidine and EdU incorporation in VSMCs. We observed a significant increase in (3)H-thymidine incorporation 24 h after a serum challenge in the geminin-RNAi-lentiviral vector group (4401.38 ± 438.39 cpm/mg), versus the non-targeting geminin-lentiviral vector (2836.88 ± 476.18 cpm/mg) and control groups (3069.50 ± 508.18 cpm/mg; P < 0.05). In the geminin-RNAi-lentiviral vector group, the EdU-positive cell rate was significantly increased (0.75 ± 0.03; P < 0.05), versus the non-targeting geminin-lentiviral vector (0.41 ± 0.0) or control group (0.40 ± 0.03). Geminin promoted VSMC proliferation, accelerating G0/G1-S cell-cycle progression (G0/G1 cells, 10 % decrease; S-phase cells, approximate 6 % increase) 12 h after serum withdrawal. Both CDK1 protein and mRNA expression were significantly increased in the positive group versus the controls. The immunofluorescence and co-immunoprecipitation results revealed a close interaction existed between CDK1 and the geminin gene in VSMC proliferation. CONCLUSIONS: Geminin gene inhibition could augment VSMC proliferation by increasing CDK1 expression; thus, geminin may be a potential target for treating vascular diseases, specifically VSMCs.

The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections.

Mical is a reduction-oxidation (redox) enzyme that functions as an unusual F-actin disassembly factor during Drosophila development. Although three Molecule interacting with CasL (MICAL) proteins exist in vertebrate species, their mechanism of action remains poorly defined and their role in vivo unknown. Here, we report that vertebrate MICAL-1 regulates the targeting of secretory vesicles containing immunoglobulin superfamily cell adhesion molecules (IgCAMs) to the neuronal growth cone membrane through its ability to control the actin cytoskeleton using redox chemistry, thereby maintaining appropriate IgCAM cell surface levels. This precise regulation of IgCAMs by MICAL-1 is essential for the lamina-specific targeting of mossy fibre axons onto CA3 pyramidal neurons in the developing mouse hippocampus in vivo. These findings reveal the first in vivo role for a vertebrate MICAL protein, expand the repertoire of cellular functions controlled through MICAL-mediated effects on the cytoskeleton, and provide insights into the poorly characterized mechanisms underlying neuronal protein cell surface expression and lamina-specific axonal targeting.

ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN.

Mutations in the RNA binding protein fused in sarcoma/translated in liposarcoma (FUS/TLS) cause amyotrophic lateral sclerosis (ALS). Although ALS-linked mutations in FUS often lead to a cytosolic mislocalization of the protein, the pathogenic mechanisms underlying these mutations remain poorly understood. To gain insight into these mechanisms, we examined the biochemical, cell biological and functional properties of mutant FUS in neurons. Expression of different FUS mutants (R521C, R521H, P525L) in neurons caused axonal defects. A protein interaction screen performed to explain these phenotypes identified numerous FUS interactors including the spinal muscular atrophy (SMA) causing protein survival motor neuron (SMN). Biochemical experiments showed that FUS and SMN interact directly and endogenously, and that this interaction can be regulated by FUS mutations. Immunostaining revealed co-localization of mutant FUS aggregates and SMN in primary neurons. This redistribution of SMN to cytosolic FUS accumulations led to a decrease in axonal SMN. Finally, cell biological experiments showed that overexpression of SMN rescued the axonal defects induced by mutant FUS, suggesting that FUS mutations cause axonal defects through SMN. This study shows that neuronal aggregates formed by mutant FUS protein may aberrantly sequester SMN and concomitantly cause a reduction of SMN levels in the axon, leading to axonal defects. These data provide a functional link between ALS-linked FUS mutations, SMN and neuronal connectivity and support the idea that different motor neuron disorders such as SMA and ALS may be caused, in part, by defects in shared molecular pathways.

Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats.

The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4- to 5-week-old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signaling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.

[Managements of open wounds from an earthquake].

OBJECTIVE: To explore the surgical managements of open wounds from 5·12 Wenchuan Earthquake. METHODS: In this report, fifty one patients with open wounds were treated after transported into West China Hospital from May 12 to 26 in 2008 after 5·12 Wenchuan Earthquake. Among 51 cases, open wounds were due to open fractures (n = 8), fasciotomy (n = 6), exposed bone (n = 8) and defects of skin and soft tissue (n = 29). All cases had wound infections. Sixty operations were performed, including muscle and myocutaneous flap (n = 4), skin grafting (n = 30), NPWT (negative pressure wound therapy) (n = 2) and debridement (n = 24). RESULTS: Four cases of muscle and myocutaneous flaps survived with an excellent blood circulation. And 30 cases of skin grafting had a survival rate of over 90%, 2 cases of NPWT and 24 cases of debridement required further treatment. CONCLUSION: With adequate surgical managements, open wound healing from an earthquake may be accelerated and the functions maximally preserved.

[Current situation of negative-pressure wound therapy].

Negative-pressure wound therapy (NPWT) has been used to help wound healing since early 1970s, and it has been used increasingly for treating a wide variety of wounds since the early 1990s and started to popularize in China near the mid 1990s. This technique is different from conventional dressing change, as it controls local humidity, alleviates edema, and improves local circulation all by negative pressure. The method generally involves the application of a dressing on the wound surface, connecting the dressing to a vacuum pump through a tube, and then sealing the wound with adhesive films. Most of the clinicians in China believe that NPWT is helpful in accelerating wound healing, though as yet there is no strong evidence to support it. Therefore, it is necessary to conduct more research to further clarify the mechanism and therapeutic effect of NPWT.

MICALs in control of the cytoskeleton, exocytosis, and cell death.

MICALs form an evolutionary conserved family of multidomain signal transduction proteins characterized by a flavoprotein monooxygenase domain. MICALs are being implicated in the regulation of an increasing number of molecular and cellular processes including cytoskeletal dynamics and intracellular trafficking. Intriguingly, some of these effects are dependent on the MICAL monooxygenase enzyme and redox signaling, while other functions rely on other parts of the MICAL protein. Recent breakthroughs in our understanding of MICAL signaling identify the ability of MICALs to bind and directly modify the actin cytoskeleton, link MICALs to the docking and fusion of exocytotic vesicles, and uncover MICALs as anti-apoptotic proteins. These discoveries could lead to therapeutic advances in neural regeneration, cancer, and other diseases.

MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis.

MICALs (molecules interacting with CasL) are atypical multidomain flavoenzymes with diverse cellular functions. The molecular pathways employed by MICAL proteins to exert their cellular effects remain largely uncharacterized. Via an unbiased proteomics approach, we identify MICAL-1 as a binding partner of NDR (nuclear Dbf2-related) kinases. NDR1/2 kinases are known to mediate apoptosis downstream of the mammalian Ste-20-like kinase MST1, and ablation of NDR1 in mice predisposes the mice to cancer as a result of compromised apoptosis. MST1 phosphorylates NDR1/2 kinases at their hydrophobic motif, thereby facilitating full NDR kinase activity and function. However, if and how this key phosphorylation event is regulated are unknown. Here we show that MICAL-1 interacts with the hydrophobic motif of NDR1/2 and that overexpression or knockdown of MICAL-1 reduces or augments NDR kinase activation or activity, respectively. Surprisingly, MICAL-1 is a phosphoprotein but not an NDR or MST1 substrate. Rather, MICAL-1 competes with MST1 for NDR binding and thereby antagonizes MST1-induced NDR activation. In line with this inhibitory effect, overexpression or knockdown of MICAL-1 inhibits or enhances, respectively, NDR-dependent proapoptotic signaling induced by extrinsic stimuli. Our findings unveil a previously unknown biological role for MICAL-1 in apoptosis and define a novel negative regulatory mechanism of MST-NDR signaling.

Semaphorin signaling: progress made and promises ahead.

Semaphorins were initially characterized according to their role in repulsive axon guidance but are now recognized as crucial regulators of morphogenesis and homeostasis over a wide range of organ systems. The pleiotropic nature of semaphorin signaling and its implication in human disease has triggered an enormous interest in the receptor and intracellular signaling mechanisms that direct the cell-type-specific and diverse biological effects of semaphorins. Recent breakthroughs in our understanding of semaphorin signaling link integrin and semaphorin signaling pathways, identify novel ligand-receptor interactions and provide insight into the cellular and molecular bases of bifunctional and reverse signaling events. These discoveries could lead to therapeutic advances in axonal regeneration, cancer and other diseases.

[Influence of intravenous infusion of D-fructose on post-operative blood glucose level in burn patients].

OBJECTIVE: To investigate the influence of intravenous infusion of 50 g/L fructose on post-operative blood glucose level in burn patients, and to evaluate its therapeutic value and safety. METHODS: A prospective, randomized, double blinded clinical trial was conducted. Forty-one burn patients with burn area ranging between 10% -30% of total body surface (TBSA) and third degree burns ranging between 1% -10% TBSA were enrolled in the study and randomized into experiment group (E, n = 21, with intravenous infusion of 500 ml of 50 g/L fructose daily for 3 days after escharectomy) and control group ( C, n = 20, with intravenous infusion of glucose 1 day after escharectomy for 3 days). Intravenous infusion of other carbohydrate liquids or oral intake of sugar was withhold within 4 hours of fructose or glucose infusion. Physical signs and side effects were observed during the administration. The plasma glucose contents before operation and on 1, 2 and 3 post-operation day( POD) were measured. The serum content of lactic acid, uric acid, hepatic and renal function were determined before operation and on 4 POD. RESULTS: Physical signs before and after drug administration, and plasma glucose content before operation, as well as before and after fructose administration in 3 POD exhibited no obvious difference between the two groups ( P > 0. 05 ). The plasma glucose content was increased 3 days after operation in the control group, and it reached the peak on 3 POD [ (8. 4+/-3. 5) mmol/L] , which was markedly higher than that before glucose administration [ (6. 4+/-2.4) mmol/L, P <0. 01) ]. The plasma contents of lactic acid and uric acid showed no obvious difference ( P >0.05) between the two groups, and also no difference before and after operation ( P > 0. 05). No changes were observed in hepatic and renal functions. CONCLUSION: Intravenous infusion of 50 g/L D-fructose is safe because it exerts little influence on blood glucose level.

The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial.

BACKGROUND: This research was conducted to evaluate the effect of enterally administered glutamine (gln) dipeptide on metabolic, gastrointestinal, and outcome parameters after severe burn injury. METHODS: Forty thermally injured patients with total body surface burns ranging between 50% and 80%, and third-degree burns ranging between 20% and 40% and without respiratory injuries, were randomized into a prospective, double-blind, controlled clinical trial. One group received gln-enriched enteral nutrition and the other group received the standard enteral formulation. Tube feedings were initiated on postburn day 1 (PBD +1), and isocaloric and isonitrogenous feedings were administered to both groups until PBD +12. The gln was given as the dipeptide of alanyl-gln (Ajinomoto, Tokyo, Japan), which provided 0.35 g gln/kg body weight/d. Plasma amino acid profiles, serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (which reflects gut permeability) were measured at specific times throughout the clinical course. Wound healing at day 30 was assessed, and length of hospital stay and total costs were determined at discharge. RESULTS: The 2 groups were similar in terms of age and extent of injury. Plasma gln concentrations were approximately 300 umol/L in both groups on PBD +1 and remained low in the control group (399 +/- 40 umol/L, mean +/- SD) but increased toward normal in the supplemented group to 591 +/- 74 (p = .048). Lactulose/mannitol ratios were increased above normal on POD +1 (control, 0.221 +/- 0.169; gln, 0.268 +/- 0.202; not significant), reflecting increased intestinal permeability after burn injury. On POD +3, the ratio in the gln group was lower than control (0.025 +/- 0.008 versus 0.049 +/- 0.016; p = .0001), and both groups returned toward normal ratios with time. Endotoxin levels on PBD +1 were elevated in both groups (control, 0.089 +/- 0.023 EU/mL; gln, 0.103 +/- 0.037 EU/mL; NS) but decreased significantly on PBD +3 in the patients receiving gln. Hospital stay was significantly shorter in the gln group than controls (67 +/- 4 days versus 73 +/- 6; p = .026). On day 30, wound healing was 86% +/- 2% complete in the gln group compared with 72% +/- 3% in controls (p = .041). Total cost of hospitalization was 62794 +/- 6178 RMB (dollar 7593 +/- 747 US dollars) in the gln group and 68996 +/- 8620RMB (dollar 8343 +/- 1042, p = .031) in controls, although the cost of the enteral nutrition was higher in the gln-supplemented patients. CONCLUSION: Enteral gln supplementation using a commercially available dipeptide supported plasma gln levels, improved gut permeability, and initially decreased plasma endotoxin levels in severely thermally injured patients. These alterations were associated with a reduction in the length of hospitalization and lower costs.