As an important component of the “neurovascular unit”,astrocytes provide protective effect for nervous through intaking excessive excitatory amino acids,providing energy substances,maintaining extracellular K + and water balance,scavenging oxygen free radicals and secreting neurotrophic factor during ischemic stroke.This article elaborates the mechanisms of astrocytes participating in ischemic stroke in recent years.

Objective To investigate the protective effects of lipsomal clodronate on renal injury in rats with severe acute pancreatifis and the assessment of renal injury. Method Totally 48 rats were randomly divided into three group:normal control group (C);SAP group, in which rats were treated with pure liposomal (P);treatment group, in which SAP rats were treated with liposomal clodronate disodium(T). The SAP model of rat was induced by injection of 5 % sodium taurochohte beneath the pancreatic membrane. Rats of normal control group received isovolumetric injections of 0.9% physiological saline solution instead of sodium taurocholate. Blood samples were collected to measure AMS,BUN,Cr,IL-6 and IL-12 at 2 hors, 6 hours after SAP. At the same time, the samples of pancreatic and renal tissues were taken for observing the pathological changes. Results Compared with controlgroup, serious renal and pancreatic damages were found in group P, and the AMS, BUN, Cr levels elevated signifi-candy (P < 0.01). Compared with group P,the renal and pancreatic damages were attenuated in group T, and the levels of Cr and AMS decreased significantly (P < 0.01), and the IL-6, IL-12 were decreased at 2 hours and 6 hours (P < 0.01). The BUN decreased significantly at6 hours (P < 0.05). Conciusions Excessive release of inflammatory mediator play an important role in renal injury in SAP. Lipsomal clodronate disodium can alleviate the damage of pancreas and kidney.

Objective To investigate the effects of Saussurea involucrata extract pretreatment on the expression of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) in focal cerebral ischemia/reperfusion in mice and its possible neuroprotective mechanism.Methods Seventy-two Kunming mice were randomly divided into four groups:sham operation,saline,Saussurea involucrata extract,and edaravone groups (n =18 in each group).Saussurea involucrata extract 0.8 g/kg was given intraperitoneally in the Saussurea involucrata extract group; edaravone 3 mg/kg was given in the edaravone group; and the same volume of saline was given in the saline group.A model of middle cerebral artery occlusion (MCAO) was induced after 7 days of continuous injection.Cerebral infarct volume was determined by 2,3,5-triphenyltetrazolium staining.Immunohistochemical staining was used to detect TLR4-positive cells in ischemic brain tissue.Reverse transcriptase polymerase chain reaction was used to detect the expression of TLR4/NF-κB mRNA.Results The cerebral infarct volume in mice in the saline,Saussurea involucrata extract and edaravone groups was 131.55± 28.25 mm3,84.10 ±13.92 mm3 and 65.10 ± 6.78 mm3,respectively.There were significant difference (F =10.158,P =0.012).The infarct volume in the Saussurea involucrata extract group (P =0.020) and edaravone group (P0.005) was significantly less than that in the saline group,and there was no significantly difference between the 2 groups.The numbers of cortex and TLR4 positive cells in hippocampus area at the ischemic sides in the saline group were significantly more than those in the sham operation group (all P ＜0.001).The numbers of positive cells of cortex and TLR4 in the Saussurea involucrata extract group and the edaravone group were significantly decreased compared to the saline group (all P ＜ 0.05),and there was no significant differences between the Saussurea involucrata extract group and the edaravone group.The expressions of TLR4,p50,and p65 mRNA in the saline group were significantly up-regulated compared to the sham operation group (all P =0.000).Saussurea involucrata extract could significantly down-regulate the expressions of TLR4,p50,and p65 mRNA at 24 hours after ischemia/reperfusion (all P =0.000).Edaravone could significantly down-regulate the expressions of TLR4 and p65 mRNA (all P =0.000) and it had a down-regulated trend for the expression of p50 mRNA (P =0.053); while there was no significant difference in the expressions of TLR4 and p65 mRNA between the Saussurea involucrata extract group and the edaravone group.Conclusions Saussurea involucrata extract pretreatment may significantly reduce the cerebral infarct volume,down-regulate the expressions of TLR4 and NF-κB subunit,and play a neuroprotective effect by inhibiting inflammatory response after ischemia.

Objective To investigate the protective effect of lipsomal clodronate against hepatic injury in rats with acute necrotizing pancreatitis (ANP). Methods 48 SD rats were randomly divided into control group, ANP group and lipsomal clodronate group, respectively. The models of ANP were established by injection of sodium taurocholate into the pancreatic capsule. Lipsomal clodronate was prepared by means of thin film. Blank liposomes and clodronate-containing liposomes was injected via caudal vein in ANP group and lipsomal clodronate group, respectively. The rats were sacrificed at 2, 6 h after ANP induction, the serum levels of ALT, AST and AMS, IL-6,IL-12 were measured, and pathologic changes of liver and pancreas were observed. Results At 6 h, serum level of ALT was (73 ± 11) U/L, (257 ± 33) U/L and (184 ± 29) U/L in control group, ANP group and lipsomal clodronate group, respectively;serum levels of AST were (190 ± 32)U/L, (590 ± 70)U/L and (430±52)U/L, respectively;serum levels of AMS were (814±80)U/L, (5031 ± 471) U/L and (2843 ± 236) U/L, respectively, serum levels of IL-6 were (26.7 ± 5.7) pmol/L, (218.0 ±4.7)pmol/L and (112.3 ± 8. O) pmol/L, respectively;serum levels of IL-12 were (4. 2 ± 1.0) pmol/L,(309.5 ± 8.5) pmol/L and (153.7 ± 6.3) pmol/L. The values in ANP group and lipsomal clodronate group were significantly higher than those in control group, while the values in lipsomal clodronate group were significantly lower than those in ANP group (P < 0. 01). Pathologic changes of liver and pancreas were significantly attenuated in lipsomal clodronate group. Conclusions Intravenous liposomal clodronate could exert protective effects on the hepatic injury in rats with ANP.

Purpose To investigate the location and distribution of EV71 receptors scavenger receptor class B member 2 ( SCARB2 ) and human P-selectin glycoprotein ligand-1 (PSGL-1) in lung tissues of fatal hand, foot and mouth disease (HFMD), healthy children and adults. Methods The expression of EV71 receptors SCARB2 and PSGL-1 was detected by using immunohistochemistry in lung tissues of 15 autopsies of HFMD, 3 of healthy children, 8 of healthy adults. Results SCARB2 distributed in bronchial, bronchioli ep-ithelia, alveolar epithelial cells and inflammatory cells among HFMD, healthy children and adults. No significant difference was noted of the positive rates of SCARB2 expression among these three groups (P>0. 05). PSGL-1 distributed in bronchial and bronchioli epi-thelium of adults, but no PSGL-1 expression was found in HFMD and healthy children. The positive rates of PSGL-1 were 100%, 0, 0 in bronchial and bronchioli epithelium among the three groups, respectively (P<0. 05). The positive rates of PSGL-1 were 100%, 66. 7%, 100% in inflammatory cells among HFMD, healthy children and adults, respectively. No significant difference was noted of PSGL-1 expression among the three groups (P>0. 05). Further, no PSGL-1 expression was observed in alveolar epithelia cells of all groups tested. Conclusions EV71 receptor SCARB2 distributes in bronchial, bronchioli, alveolar epithelial and inflammatory cells of HFMD. Meanwhile, PSGL-1 only distributes in inflammatory cells of HFMD, suggesting that SCARB2 possibly plays a role on HFMD infection.

Objective To investigate the protective effect of clodronate SPIO liposomes on liver injury of rats with severe acute pancreatitis(SAP)and the role of MRI in evaluating the extent of liver injury.Methods Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation.Clodronate-SPIO-containing liposomes was prepared by the thin-film method.SAP models were prepared by a uniform injection of sodium taurocholate(2 ml/kg body weight)into the subcapsular space of the pancreas.SD rats were randomly divided into control group,SAP plus SPIO group, and clodronate-SPIO-containing liposome group.Six hours after SAP models were available,T2-weighted MRI scanning(in the same plane)of the liver of rats in each group were performed.At the end of the scanning,blood samples were taken from the supcrior mesenteric vein to measure the contents of serum ALT and AST.Meanwhile, The pathological changes in the liver and pancreas were observed.Results Transmission electron microscopic examination showed that liposomes had a uniform size.No changes in the pancreas of rats in control group were noted.The pathological changes in the pancreas and liver of rats in SAP plus clodronate-SPIO-containing liposome group were significantly milder than those in SAP plus SPIO liposome group.The contents of serum ALT and AST in rats in SAP plus SPIO liposome group were significantly higher than those in control group(P＜0.01), while the contents of serum ALT and AST in rats in SAP plus clodronate-SPIO-containing group were significantly lower than those in SAP plus SPIO liposome group(P＜0.01).The MRI signal intensity of the liver in SAP plus SPIO liposome group and SAP plus clodronate-SPIO-containing liposome group was significantly lower than that in control group.The significant changes in the MRI signal intensity of the liver in SAP plus SPIO liposome group and SAP plus Clodronate-SPIO liposome group were noted(P＜0.01).Conclusion Clodronate-containing liposomes have protective effects against liver injury in SAP rats and SPIO can be used as a tracer for MRI examination.

Objective: To observe the impact of cardiac contractility modulation (CCM) on myocardial remodeling in rabbit model of chronic heart failure (CHF) with its possible mechanism. Methods: Rabbit HF model was established by ascending aortic root ligation; the animals were divided into 3 groups: Sham group, the animals received thoracotomy without aortic ligation, HF group and HF+CCM group, the HF animals received CCM treatment for 4 weeks. n=10 in each group. Cardiac function was measured by echocardiography at 12 and 16 weeks in each group respectively; myocardial tissue fibrosis and pathological changes were examined by Masson staining; plasma BNP level was assessed by ELISA; protein expressions of collagen I, collagen II, MMP2,MMP9, TIMP1 and galectin-3 in myocardial tissue were determined by Western blot analysis. Results: ① By echocardiography: with 12 weeks treatment, compared with Sham group, HF group and HF+CCM group had increased LVESD, LVEDD and decreased LVFS, LVEF, all P<0.05; with 16 weeks treatment, compared with HF group, HF+CCM group had improved LVESD, LVEDD, LVEF and LVFS, all P<0.05. ② Pathological changes:compared with Sham group, HF group showed increased collagen content in myocardial tissue, P<0.05; CCM treatment could partially decrease collagen accumulation, P<0.05. ③ After 12 weeks treatment, compared with Sham group, HF group and HF+CCM group presented elevated plasma BNP level, P<0.05; after 16 weeks treatment, compared with HF group, HF+CCM group presented reduced plasma BNP, while it was still higher than that in Sham group, P<0.05. ④ By Western blot analysis: compared with Sham group, HF group demonstrated increased protein expressions of collagen I, collagen II, MMP2, MMP9, TIMP1 and galectin-3 in myocardial tissue; the above indexes were much lower in HF+CCM group while still higher than those in Sham group, all P<0.05. Conclusion: CCM could improve myocardial remodeling in rabbit model of CHF which might be related to down-regulated protein expressions of collagen I, collagen III, MMP2, MMP9, TIMP1 and galectin3 in myocardial tissue.

AIMTo investigate the effects of RLI on plasma nitric oxide (NO) and NO synthase (NOS) isoforms of healthy humans.

METHODS30 healthy human subjects (aged from 40 - 70 years old) were recruited. RLI was induced by five 5 min cycles of ischemia of non dominant arm (200 mmHg, 5 min interval). Blood pressure, heart rate, and the feelings of ischemic arm were continuously monitored. Venous plasma was collected in contralateral arm at Pre, Post-0 h, Post-4 h, and Post-24 h. Plasma level of NO was measured by Griess reaction, and NOS was measured by chemical method.

RESULTSBlood pressure and heart rate varied in normal range. The uncomfortable feeling was decreased with the increasing numbers of ischemic cycles. Plasma level of NO, and iNOS in plasma were significantly increased at Post-0 h, Post-4 h, and Post-24 h compared to Pre (P < 0.05). tNOS was also significantly increased at Post-0 h and Post-4 h compared to Pre (P < 0.05). No significant change in plasma cNOS was shown at following three time points than Pre.

CONCLUSIONThese findings suggest that RLI can elevate plasma level of NO, tNOS, and iNOS in healthy humans. RLI might be a safe method as a rIPC, and it would have important possibility to be performed in clinic.

Adult ; Aged ; Arm ; blood supply ; Female ; Humans ; Ischemia ; blood ; physiopathology ; Ischemic Preconditioning ; methods ; Male ; Middle Aged ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; metabolism ; Reperfusion Injury ; physiopathology ; prevention & control

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.