Mechanism of 1,2-dichloroethane-induced toxicity in SH-SY5Y Cells / 中国职业医学

OBJECTIVE: To establish the cell model of human neuroblastoma cell( SH-SY5Y cell) exposed to1,2-dichloroethane( 1,2-DCE) in vitro and to explore the mechanism of 1,2-DCE-induced toxicity in SH-SY5Y cells.METHODS: SH-SY5Y cells were collected in their logarithmic growth phase and cultured in complete medium that had final concentrations of 1,2-DCE in 0,10,20,30,40,50,60,70 and 80 mmol / L for 24 hours. Cell morphology was observed and cell survival rate was examined by CCK-8 assay. Using chemical colorimetric method, the activity of lactic dehydrogenase( LDH) in the cell culture supernatant,and the intracellular level of malondialdehyde( MDA),the intracellular activities of superoxide dismutase( SOD) and adenosine triphosphate( ATP) enzymes were detected. RESULTS: With the increasing exposure concentrations of 1,2-DCE,the cell density of SH-SY5Y cells gradually decreased,the synapse became shorter,the membrane ruptured,cytoplasm condensed and cytoplasmic contents overflowed increased.With the increasing concentration of 1,2-DCE,the cell survival rate decreased( P < 0. 01),the activity of LDH in the cell culture supernatant increased( P < 0. 01). These changes had a dose-effect correlation. Intracellular MDA level,and activities of SOD,Na~+-K~+-ATP enzyme,Ca~(2+)-Mg~(2+)-ATP enzyme and total ATP enzyme increased at first and then decreased. The activity of LDH in the cell culture supernatant and cell survival rate was negatively correlated( the correlation coefficient is- 0. 907,P < 0. 01). CONCLUSION: 1,2-DCE could inhibit the proliferation of SH-SY5Y cells.The mechanism may be related to the permeability change of cell membrane,cellular damage from excessive free radicals,the decrease of free radical scavenging capacity,ATP enzyme activity and calcium overloading. SH-SY5Y cells can be used as a common cell line for 1,2-DCE cytotoxicity analysis.

Changes of the immunological barrier of intestinal mucosa in rats with sepsis / 世界急诊医学杂志（英文）

BACKGROUND:Sepsis has become the greatest threat to in-patients, with a mortality of over 25％.The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture. METHODS:Sixty Sprague-Dawley rats were randomly divided into a sepsis group (n=45) and a control group (n=15). The rats in the sepsis group were subjected to cecal ligation and puncture (CLP), whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 (RD-5) and trefoil factor-3 (TFF3) mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected. RESULTS:The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased (P<0.05) in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group (P<0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52). In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group. CONCLUSION:The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.

Expressions of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death / 世界急诊医学杂志（英文）

BACKGROUND:As the regulators of cytokines, suppressors of cytokine signaling (SOCS) play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death (SCD).METHODS:Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 died of acute myocardial infaction (MI group), and 8 died from traffic accidents and trauma (control group). The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 software and the data were analyzed by ANOVA.RESULTS:The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[(0.788±0.101), (0.741±0.111) vs. (0.436±0.044), (P<0.01); (0.841±0.092), (0.776±0.070) vs. (0.454±0.076), (P<0.01)] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(320.00±48.48), (347.14±70.88) vs. (42.50±10.35), (P<0.01)] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(381.11±59.25) vs. (40.00±10.69), (P<0.01)] and[(332.86±111.91) vs. (40.00±10.69), (P=0.001)].CONCLUSION:The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.

Breast cancer resistance protein expression and 5-fluorouracil resistance / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To filtrate breast cancer resistance protein (BCRP)-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance.</p><p><b>METHODS</b>MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography (HPLC) assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immunohistochemistry (IHC) were employed to investigate the BCRP expression in breast cancer tissue specimens.</p><p><b>RESULTS</b>MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil (5-Fu) (P<0.05, n=3) in the cell model, while HPLC assay indicated that the intracellular retention dose of 5-Fu was significantly correlated with the expression of BCRP (r=-0.897, P<0.05, n=3). A total of 140 breast cancer tissue specimens were collected. BCRP-positive expression was detected in forty-seven specimens by both RT-PCR and IHC. As shown by MTT assay subsequently, the resistance index (RI) of 47 BCRP-positive breast cancer tissue specimens to 5-Fu was 7-12 times as high as that of adjacent normal tissue samples. BCRP expression was related to 5-Fu resistance (R2=0.8124, P<0.01).</p><p><b>CONCLUSION</b>Resistance to 5-Fu can be mediated by BCRP. Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.</p>

Risk factors for death due to fungal septicemia and prognostic analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the incidence, clinical features and the predisposing factors of fungal septicemia, and investigate the risk factors for death due to fungal septicemia and the prognosis of the patients.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 91 patients with fungal septicemia diagnosed in the last 17 years, including 60 patients with clinical cure or improvement, and 31 who die of the disease. Based on the results by univariate analysis, the data were analyzed using logistic multiple regression and Fisher's discriminant analysis.</p><p><b>RESULTS</b>Fungal septicemia had many predisposing factors with high mortality rate. Univariate analysis revealed significant differences between the cured/improved cases and the fatal cases for 12 variables, including advanced age, complication by bacterial infection, septic shock, multiple organ dysfunction syndrome (MODS), ICU patients, cortical hormone therapy, surgery, chemotherapy, use of immunopotentiating agents, length of hospital stay before antifungal therapy, time of anti-fungus therapy and types of invasive procedures. Logistic multiple regression analysis showed that the types of invasive procedures, MODS, surgery and prolonged hospital stay before antifungal therapy were the independent risk factors for fungal septicemia-related death. Fisher's linear discriminant equation was established for predicting the prognosis of the disease.</p><p><b>CONCLUSION</b>The types of invasive procedure, MODS, surgery and prolonged hospital stay before antifungal therapy are the independent risk factors for fungal septicemia-related death, and the patients' prognosis can be predicted using Fisher's linear discriminant equation.</p>

Effects of ulinastatin on gut mucosal apoptosis and bacterial translocation in rats with sepsis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of ulinastatin on gut mucosal apoptosis and bacterium translocation in a rat model of sepsis.</p><p><b>METHODS</b>Fifty rats were randomly assigned into 4 groups, namely the control (n=5, no operation or drugs), ulinastatin pretreatment (n=15, treated with 25,000 U/kg ulinastatin 2 h before operation), ulinastatin treatment (n=15, treated with 25,000 U/kg ulinastatin 2 h after operation) and sepsis model (n=15, without drug treatment) groups. The rats in the later 3 groups were subjected to cecal ligation and puncture (CLP). At 3, 6 and 12 h after CLP, the rats were sacrificed and the ileum was removed to examine the pathology and apoptosis of the mucosa. The DNA of Bacillus coli in the whole blood was detected using PCR.</p><p><b>RESULTS</b>Sepsis caused of epithelial cell loss in the ileal villi, ulceration and blebbing of the lamina propria. Ulinastatin treatment administered before and after the operation both significantly alleviated these morphological anomalies. The sepsis rats showed significantly increased intestinal mucosal apoptotic index as compared with the other 3 groups (P<0.05). Ulinastatin pretreatment, in comparison ulinastatin treatment 12 h after CLP, significantly increased the intestinal mucosal apoptotic index (P<0.05). Bacillus coli DNA was positive in sepsis and postoperative ulinastatin treatment groups but negative in the control and pretreated groups.</p><p><b>CONCLUSION</b>Increased intestinal musocal apoptosis and gut bacterial translocation occur in rats following sepsis, and ulinastatin can effectively decrease intestinal mucosal apoptosis and inhibit bacterial translocation.</p>

Analysis of acute cerebral arterial thrombosis with multiple organ dysfunction syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the incidence, case fatality and risk factors of acute cerebral arterial thrombosis complicated by multiple organ dysfunction syndrome (MODS).</p><p><b>METHODS</b>A retrospective study was conducted in 830 patients with acute cerebral arterial thrombosis, among whom 89 also developed MODS.</p><p><b>RESULTS</b>The incidence of MODS in these patients was 10.7% with case fatality of 58.4%. The presence of concurrent infection and increased number of organ involved both resulted in higher case fatality. The preceding health status, number of failing organs and score of neurologic impairment were the main fetal factors according to logistic regression analysis.</p><p><b>CONCLUSION</b>MODS usually occurs in two weeks after the onset of acute cerebral arterial thrombosis. Prevention of MODS involves rigorous treatment of the compromised organs and comprehensive systemic therapy in addition to the management of the primary diseases.</p>

Effects of biphasic square waveform with different energy levels on external defibrillation / 中华急诊医学杂志

Objective To compare the effects of biphasic square waveform (BSW) with low or high energy on external defibrillation.Method Adult swine model of closed chest ventricular fibrillation induced by electricity was established.Eighteen swine,weighing (30?3.3) kg were randomly divided into three groups:50-50-50 J group (n=6),30-50-75 J group (n=6),120-150-200 J (n=6).After three minutes of ventricular fibrillation without treatment,the pigs in the three groups were defibrillated accordance to the above sequences. Results 30 J BSW didn't succed to external defibrillate.The first defibrillation successful rate of 50 J and 120 J BSW was 5/6.The total defibrillation successful rate of every group was 100%.All pigs quickly had spontaneous circulation after defibrillation and survived more than 24 hours.ST-T change of low-energy was less than that of high-energy.After resuscitation,myocardial function decreased,but there had not significant differences between groups.Conclusions In the study,30J BSW could not reach successful defibrillation,and 50 J and 120 J BSW had similar defibrillation efficacy.The ideal energy of BSW external defibrillation was 50 J.

The effect of Ulinastatin on the delivery of cytokines in patients with septic shock / 中华急诊医学杂志

Objective To investigate the effect of Ulinastatin on the delivery of cytokines in patients with septic shock.Methods It was a prospective and controlled clinical study.Seventy-eight patients with septic shock were randomly divided into control group and treatment group and thirty-nine in every group.Patients in treatment group received Ulinastatin 200 000 units intravenous everyday for 3 days,while those in control group received equal volume of normal saline as placebo.At different time points (at 24 th,48 th,72 th hour after start of treatment),the levels of tumor necrosis factor-alpha (TNF-?),interleukin-1 (IL-1),interleukin-6 (IL-6 ),interleukin-8 (IL-8) and superoxide dismutase (SOD) in serum were assayed.Results In comparison with control group,the levels of TNF-?,IL-1,IL-6,IL- 8 of treatment group decreased markedly (P＜0.05,P＜0.01) at different time points,whereas the level of SOD was higher markedly (P＜0.05,P＜0.01) at various time points.Conclusion Ulinastatin has protective effect on patients with septic shock through decreasing the levels of TNF-?,IL-1,IL-6,IL-8 and increasing in the level of SOD.

Effect of goblet cell in rat intestine on the restitution process of the gut barrier after hemorrhagic shock / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the changes of the goblet cells in the intestine during the restitution process of the gut barrier after hemorrhagic shock.</p><p><b>METHODS</b>Forty-nine Sprague-Dawley rats with body weight of 250-300 g were divided into control group (n=7) and experimental group (n=42). Rats in the experimental group was further divided into 6 groups (n=7 each) according to different time point at 1, 3, 6, 12, 24, and 36 hours after hemorrhagic shock resuscitation. The specimens from ileum tissue were taken to observe the morphological chan ges of the intestinal mucosa. The number of goblet cells was determined by light microscope and/or electron microscope. The contents of trefoil factor family 3 (TFF3) of goblet cells were examined using GC-9A gas chromatographic instrument.</p><p><b>RESULTS</b>After hemorrhagic shock, mucosal epithelial injury was obvious in the small intestine. Tissue restitution was found after 3 hours, and mostly established after 12 hours. Following tissue restitution,the denuded mucosal surface was covered intensively by goblet cells. The number of goblet cells on the intestinal mucosa was reduced significantly from 243+/- 13 at 1 h to 157+/- 9 at 24 h (r=- 0.910, P< 0.01), and returned to normal level at 36 h. In the experimental group, the content of TFF3 in the intestinal mucosa increased significantly at 12 hours, decreased, but was still higher at 24 hours (t=3.24, P< 0.05).</p><p><b>CONCLUSIONS</b>The goblet cells play a key role in the restitution of intestinal mucosa. High expression of TFF3 may facilitate the intestinal mucosal restitution in the early phase.</p>