Sepsis is the systemic inlfammatory response to infection and a major cause of mortality in critical patients. The severe disorder of immune system is the common pathophysiological changes in septic patients. Mesenchymal stem cells (MSCs) have shown great immunoloregulation properties in recent studies. It can increase the level of IL-10, an anti-inflammatory cytokine, promote the secretion of prostaglandin E2 (PGE2), indolamine 2,3-dioxygenase (IDO), and regulate the proliferation, differentiation and function of the immune cells such as mononuclear macrophage, t-lymphocytes, natural killer cells and so on. MSCs may provide new ideas for the treatment of sepsis.

Objective To study Xuebijing(XBJ,a Chinese herbal preparation)on heat shock protein 70(HSP 70)in rats with severe acute pancreatitis(SAP).Methods Sixty healthy male SD rats were randomly(random number)and equally divided into sham operation group(A),SAP group(B),SAP with low-dose XBJ(4 ml/kg)intervention group(C)and high-dose XBJ(8 ml/ kg)intervention group(D).The SAP model was made by retrograde infusion of 5 ％ sodium taurocholate into the bilepancreatic duct.The rats in group C and group D were treated with 4 ml/kg XBJ and 8 ml/kg XBJ injected intraperitoneally and the treatment repeated once 12 hours later.Rats were sacrificed separately 6 h,12 h and 24 hours after modeling with/without XBJ and the blood samples were collected.Serum HSP 70 and cytokines TNF-α,IL-1β,IL-6 levels were measured by using enzyme-linked immunosorbent assay (ELISA); and correlation between serum HSP 70 and cytokines was analyzed.Results Levels of serum HSP 70 and TNF-o,IL-1β,IL-6 did not change significantly in rats of group A.Compared with group B,levels of serum HSP 70 and TNF-α,IL-1 β,IL-6 in all blood samples were lower significantly in groups C and D,and levels of those biomarkers decreased much more in group D than those did in group C.Thelevels of serum HSP 70 were positively correlated with cytokines TNF-α,IL-1β and IL-6(P ＜ 0.05).Conclusions Levels of serum HSP 70 in rats with SAP increased significantly.XBJ could reduce serum HSP 70 level in rats with SAP,and this may be the mechanism of the anti-inflammatory effects of XBJ.

Objective To explore the therapeutic effects of early short time venous-venous hemofiltration(SVVH) on severe acute pancreatitis(SAP) with acute lung injury(ALI).Methods Twenty-there patients with SAP and ALI were treated by routine project,and among them twelve patients accepted SVVH therapy.During the therapy,life sign、PaO2/FiO2 and APACHEII score were registered.Results Compared with control group,the clinical representation and organ function of SVVH group meliorated. PaO2/FiO2 were raised, APACHEII score and death risk were declined.Conclusions The early short time venous-venous hemofiltration(SVVH) on severe acute pancreatitis(SAP) with acute lung injury(ALI) could improve clinical symptom ,protect the organ dysfunction and decline the death risk.

Aim Enteric microspheres were prepared to prevent the interaction of drug with gastric acid and to improve its bioavailability. Methods The enteric microspheres with a matrix structure were successfully produced using a spherical crystallization technique. Hydroxypropyl methylcellulose phthalate ( HP-55 ), an enteric material, was coprecipitated with the drug by salting-out effect during the preparation process. A mixture of water and ethanol was chosen as a good solvent and dichloromethane was used as a the first time to prepare microspheres by making the water-soluble drug and water-insoluble excipient coprecipitated. In vivo test demonstrated that the drug absorption from the enteric oleanolic acid dihemiphthalate sodium (OADHPS) microspheres was significantly prolonged compared to that with OADHPS powder after a lag-time. Furthermore, the drug bioavailability was 181.6% greater than that with the OADHPS powder. Conclusion The microspheres of water soluble drug could be prepared by using water phase replacing organic phase as poor solvent which decrease the quantity of organic solvent and benefit the environment prevention.

The splenic arteries of 110 Chinese cadavers and 65 dogs were observed with methods nf gross dissection, angiography (suspension of red lead oxide (Pb_3O_4) as the contrasr meduim) and corrosive cast (Polychloroethylene). The ramifications of the splenic artery and their relation to the splenic lobes and segments were studied. The results were outlined as follows:1. There are three patterns of splenic artery ramifications in human: Type Ⅰ, biramification(89%); Type Ⅱ, triramification(8%); and Type Ⅲ, polyramification(3%).2. In type Ⅰ, most of the splenic arteries divide into a superior and an inferior splenic lodar arteries. Most of the superior splenic lobar arteries subdivide into the superior and mid-superior segmental arteries and the inferior splenic lobar artery subdivides into the mid-inferior and inferior segmental arteries.3. All of the splenic arteries of the dogs we studied may divide into two splenic lobar arteries and each lobar artery further divides into two segmental arteries without exception.4. Between the lobar or segmental arteries there are zones poorly vascularized.5. Based on the anatomic observations we had performed experimental partial splenectomies on 15 dogs. All of the dogs survived the operation and their wound made on the spleen healed up very well.

Objective To investigate the protective effect of allicin on intestinal mucosal barrier of septic rats so as to explore the possible mechanism.Methods Twenty-four male SD rats were randomly (random number) divided into sham,septic model and allicin treatment group.Septic model was established by cecal ligation and puncture (CLP) in rats.Rats in the treatment group were administered with allicin (30 mg/kg,ip)at 6 h and 12 h after modeling,while those in the model and sham groups were treated with equal amount of saline instead.Rats were sacrificed at 24 h and the serum D-lactic acid,diamine oxidase (DAO) and fluorescence isothiocyanate-dextran (FITC-Dextran,FD-40) were determined to evaluate the intestinal mucosal barrier function.The levels of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),malondialdehyde (MDA),and the activity of superoxide dismutase (SOD) in intestinal tissue were measured.Histopathological changes of intestinal mucosa injury were assessed by Hematoxylin-eosin staining.Results Compared with the sham group,levels of serum D-lactic acid,DAO and FD-40 increased significantly in the CLP group (D-lactic acid:599.4±101.1 vs.149.2±20.63 nmoL/mL,t=11.84,P＜0.01;DAO:302.1 ±64.5 vs.76.57±14.76 ng/mL,t=9.433,P＜0.01;FD-40:6664.0±1437.0vs.1446.0±205.0 ng/mL,t =9.704,P ＜0.01);intestinal morphology damage occurred in the CLP group;intestinal levels of TNF-α,IL-6 and MDA increased greatly (TNF-αt:186.35 ±20.43 vs.58.76 ±8.94 pg/mL,t=17.23,P＜0.01;IL-6:763.25±85.23vs.125.36±14.37 pg/mL,t=22.54,P＜0.01;MDA:29.36±3.27vs.7.24±0.85 nmol/mg prot,t=16.61,P＜0.01),while SOD activity reduced (35.75±6.53 vs.73.26 ±8.35 U/rmg prot,t =10.57,P ＜0.01) in the CLP group.Allicin treatment greatly inhibited the increase of D-lactic acid,DAO and FD-40 levels in rat plasma caused by CLP (D-lactic acid:330.1 ±81.77 vs.599.4±101.1 nmol/mL,t=7.086,P＜0.01;DAO:171.8±49.70vs.302.1±64.56ng/mL,t=5.45,P＜0.01;FD-40:3349.0±1167.0 vs.6664.0±1437.0 ng/mL,t=6.165,P＜0.01);intestinal morphology damage was improved in the allicin treatment group;allicin treatment greatly inhibited the intestinal levels of TNF-o,IL-6 and MDA and preserved the intestinal SOD activity compared with the CLP group (TNF-α:95.37 ±12.68 vs.186.35 ±20.43 pg/mL,t =12.29,P＜0.01;IL-6:354.27±46.27vs.763.25±85.23pg/mL,t=14.45,P＜0.01;MDA:16.27±3.14vs.29.36±3.27 nmol/mgprot,t=9.831,P＜0.01;SOD:55.35 ±6.23vs.35.75±6.53 U/mgprot,t=5.522,P ＜0.01).Conclusions Allicin could inhibit local inflammation and oxidative stress in the intestine and exerts protective effect on intestinal mucosal barrier of septic rats.

Objective:To investigate roles of autophagy in ameliorating sepsis-induced acute lung injury by allicinin in mice.Methods:A total of 152 male Balb/c mice (8-week old) were randomly divided into a sham group,a septic model group,an allicin treatment group,and an autophagy inhibition group.Septic mouse model was established by cecal ligation and puncture (CLP).Mice in the allicin treatment group were given allicin (30 mg/kg,intra-peritoneal injection) at 6 and 12 h,while those in the autophagy inhibition group were given autophagy inhibitor 3-MA (15 mg/kg,intra-peritoneal injection) at half an hour after allicin administration.Mice in the model and sham group were administered with the same amount of saline.Twenty mice in each group were randomly chosen to observe the 7 d survival rate.The other 12 mice were killed at 24 h,and the bronchoalveolar lavage fluid (BALF) (n=6) and lung tissues (n=6) were collected.ELISA was used to detect the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF.Hematoxylin-eosin staining was preformed to show the morphological changes in the lung tissues.Malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) in the lung tissues were examined.The expression of LC3B and Beclin-1 was determined by immunohistochemical analysis.Results:Compared with the sham group,the 7 d survival rate and lung SOD activity were decreased in the CLP group (P<0.05);the lung morphological damage score,the levels of TNF-α and IL-6 in the BALF,MDA content in the lung,and expression of LC3B and Beclin-1 were increased greatly in the CLP group (P<0.05).Compared with the CLP group,the 7 d survival rate,lung SOD activity and the expressions of LC3B and Beclin-1 were increased significantly in the allicin treatment group (P<0.05);the lung morphological damage scores,the levels of TNF-α and IL-6 in the BALF and MDA content in the lung were decreased obviously in the allicin treatment group (P<0.05).Compared with the allicin treatment group,the 7 d survival rate,lung SOD activity,and the expressions of LC3B and Beclin-1 were decreased in the 3-MA group (P<0.05);the lung morphological damage scores,the levels of TNF-α and IL-6 in the BALF,and MDA content in the lung were increased significantly in the 3-MA group (P<0.05).Conclusion:Allicin may ameliorate sepsis-induced acute lung injury in mice by enhancing the level of autophagy.

AIM:To investigate the role of lipopolysaccharide binding protein (LBP) for diagnosis and prog-nosis prediction in the septic patients.METHODS:A total number of 80 ICU patients were enrolled.The patients were divided into systemic inflammatory response syndrome ( SIRS) group and sepsis group, the patients in sepsis group were di-vided into non-survivor sub-group and survivor sub-group.We collected the serum samples and analyzed acute physiology and chronic health evaluation ( APACHE) II score on the first day of the patients hospitalized in ICU.In addition, we also selected 10 healthy volunteers and collected their serum samples.The serum concentrations of LBP, C-reactive protein ( CRP) and procalcitonin ( PCT) were measured by ELISA.ROC analysis of LBP, CRP, PCT and APACHE II score was conducted to discriminate among critically ill patients with sepsis and predict the prognosis of the patients with sepsis.RE-SULTS:The levels of the 4 indicators in the septic patients were higher than those in the patients of SIRS (P<0.05).In addition, serum LBP and APACHE II score in the non-survivor sub-group were higher than those in the survivor sub-group (P<0.05), whereas no difference of the PCT and CRP levels between survivors and non-survivors with sepsis was ob-served.LBP levels greater than 26.84 mg/L had 97.1% sensitivity and 95.9% specificity to discriminate between SIRS and sepsis.LBP levels greater than 54.16 mg/L had 85.2%sensitivity and 80.0%specificity for prognosis of unfavorable outcome.CONCLUSION:LBP level was more accurately correlated with diagnosis or prognosis prediction than CRP or PCT in patients with sepsis.

To determine expression levels of glial fibrillary acidic protein in patients of sepsis-associated encephalopathy (SAE) and its clinical significance.
 Methods: Patients, admitted to intensive care units and diagnosed as sepsis, were recruited to our study from October 2016 to August 2018 in the Third Xiangya Hospital, Central South University. SAE is defined as a brain dysfunction secondary to sepsis and without evidence of a primary central nervous system infection or encephalopathy due to other reasons. The SAE group and non-SAE group were classed by Confusion Assessment Method for the ICU (CAM-ICU) score. We measured the levels of serum GFAP, S100β and neuron-specific enolase (NSE) within 24 hours after diagnosis of sepsis, and compared the patients' general clinical data, ICU stay time, 28-day and 180-day mortality.
 Results: Among 152 enrolled patients, 58 and 94 were assigned to the SAE group and the non-SAE group, respectively. There were a significantly higher Sequential Organ Failure Assessment (SOFA) scores, 28-day mortality rate, as well as 180-day mortality rate in the SAE group (all P<0.001). The levels of GFAP, NSE and S100β in the SAE group were significantly higher than those in the non-SAE group (all P<0.001). The diagnostic values of GFAP was 0.67 μg/L, with sensitivity at 75.9% and specificity at 77.7%. Area under the receiver operating characteristic curve (AUROC) of GFAP, NSE and S100β were 0.803, 0.795 and 0.750, respectively. Pearson analysis showed that serum GFAP level was positively correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II) score, but it was negatively correlated with Glasgow Coma Scale (GCS) score, 28-day survival rate and 180-day survival rate.
 Conclusion: The level of serum GFAP is significantly increased in SAE, which shows certain correlation with incidence, severity and prognosis of the disease.
APACHE ; Glial Fibrillary Acidic Protein ; blood ; Humans ; Intensive Care Units ; Organ Dysfunction Scores ; Prognosis ; ROC Curve ; Sepsis ; Sepsis-Associated Encephalopathy ; diagnosis

To investigate the effect of sinomenine on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages and the underlying mechanisms.
 Methods: The mouse RAW264.7 macrophages were treated with sinomenine and/or LPS with or without heme oxygenase-1 (HO-1) inhibitor Znpp. Real-time PCR, ELISA, immunofluenscence, and Western blot were used to detect the mRNA expression of TNF-α and IL-6, the release of TNF-α and IL-6, the protein expression of HO-1 and autophagy, respectively.
 Results: Compared with the control group, the mRNA expression and release of inflammatory cytokines TNF-α and IL-6 were increased, the green fluorescence of autophagy-related protein LC3 was accumulated and the protein expression of HO-1 was increased in RAW264.7 cells after LPS treatment (P<0.05). Compared with the LPS group, sinomenine treatment could reduce the mRNA expression and release of TNF-α and IL-6, accompanied by increasess in green fluorescence aggregation of LC3 and HO-1 production (P<0.05). HO-1 inhibitor Znpp could weaken the ability of sinomenine through suppressing TNF-α and IL-6 expression and decreasing the aggregation of LC3 green fluorescence (P<0.05).
 Conclusion: Sinomenine could alleviate LPS-induced inflammation in RAW264.7 macrophages, which might be related to HO-1 mediated autophagy. This study provides an experimental and theoretical basis for the clinical application of sinomenine in prevention and treatment of inflammation.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Autophagy ; drug effects ; Gene Expression Regulation, Enzymologic ; drug effects ; Heme Oxygenase-1 ; genetics ; Inflammation ; chemically induced ; Lipopolysaccharides ; Macrophages ; drug effects ; Mice ; Morphinans ; pharmacology