AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

AIM:To investigate the mechanism by which exosomes(EXOs)derived from neural stem cells(NSCs)pretreated with astragaloside IV(ASIV)alleviate brain damage in rats after ischemic stroke.METHODS:Rat NSCs were isolated from fetal rats within 24 h of birth,cultured for 3 d,and subsequently treated with ASIV for additional 5 d.The EXOs from untreated NSCs and ASIV-pretreated NSCs(ASIV-EXOs)were isolated via ultracentrifugation of the cell supernatant.These EXOs were characterized using Western blot to detect specific markers such as CD63,tumor sus-ceptibility gene 101(TSG101)and calnexin.Nanoparticle analysis was employed to determine the size,and the morpholo-gy of the EXOs was observed under electron microscope.Six to eight-week-old SD male rats were randomly assigned to 6 groups:sham group,middle cerebral artery occlusion/reperfusion(MCAO/R)model group,edaravone(EDA)treatment(MCAO/R+EDA)group,EXOs treatement(MCAO/R+EXOs)group and ASIV-EXOs treatment(MCAO/R+ASIV-EXOs)group.Tail vein injections were administered within 2 h following the successful establishment of the MCAO/R model.The Zea Longa method was utilized to evaluate neurological deficits,while the TTC method was employed to assess brain infarc-tion.Pathological changes were examined through HE staining,and TUNEL and caspase-1 immunofluorescence double staining were conducted to detect cellular pyroptosis.Serum levels of interleukin-1β(IL-1β)and IL-18 were measured us-ing ELISA,and Western blot was performed to evaluate the expression of caspase-1,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),gasdermin D(GSDMD),and IL-18 proteins in the ischemic area of the rat cerebral cortex across all groups.RE-SULTS:The MCAO/R group exhibited significantly higher neurological deficit scores compared to the sham group(P＜0.01)and lower scores in the administered groups relative to the MCAO/R group(P＜0.05).Cerebral infarction was mark-edly increased in the MCAO/R group compared to the sham group(P＜0.01),whereas the infarction area was reduced in the administered groups compared to the MCAO/R group(P＜0.05).Serum levels of IL-1β and IL-18 were significantly el-evated in the MCAO/R group versus the sham group(P＜0.01)and were lower in the administered groups compared to the MCAO/R group(P＜0.01).Moreover,IL-1β and IL-18 levels in the MCAO/R+ASIV-EXOs group were lower than those in the MCAO/R+EXOs group(P＜0.05).HE staining revealed pronounced sieve-like infarction foci in the ischemic area of the rat cerebral cortex in MCAO/R group,characterized by disorganized neuronal arrangements,reduced or absent Nys-trom's vesicles,shrunken or fragmented nuclei,and numerous red neurons.In contrast,drug-treated groups exhibited milder pathological changes with clearer neuronal structures and a significant reduction in red neuron counts.Immunofluo-rescence double staining indicated a significant increase in double-positive cells in the MCAO/R group compared to the sham group(P＜0.01),with a decrease in double-positive cells in the administered groups relative to the MCAO/R group(P＜0.05)and a further reduction in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).The expression levels of caspase-1,NLRP3,ASC,IL-18 and GSDMD proteins in the ischemic region of the rat cerebral cortex were significantly reduced in the administered groups compared to the MCAO/R group(P＜0.01),with further re-duction observed in the MCAO/R+ASIV-EXOs group compared to the MCAO/R+EXOs group(P＜0.05).CONCLU-SION:Exosomes derived from ASIV-pretreated NSCs attenuate brain damage in ischemic stroke rats,potentially through a mechanism involving the inhibition of pyroptosis mediated by the NLRP3/caspase-1 pathway.

Objective To explore the correlation between plasma asymmetric dimethylarginin(ADMA) and essential hyper‐tention(EH) by comparing the difference of plasma asymmetric dimethylarginine levels between Kazak and Han patients with EH in Xinjiang .Methods 91 Kazak and 112 Han patients with EH were selected .81 Kazak and 110 Han healthy people were selected as healthy control groups .The plasma ADMA levels in EH groups and the control groups were measured by using the reverse phase‐high performance liquid chromatography (RP‐HPLC) .Meanwhile the liver function ,renal function ,blood lipids ,blood glucose and fructosamine were measured .Results Kazak and Han patients with EH had higher levels of plasma ADMA than the control groups (P<0 .01);there was a positive correlation between the plasma ADMA and blood pressure levels of EH patients in two na‐tionalities(r=0 .715 ,P<0 .01 for Kazak ;r=0 .645 ,P<0 .01 for Han) .Conclusion Both Kazak and Han patients with EH have higher levels of ADMA than the respective healthy control group in Xinjiang .The correlation between the plasma levels of ADMA and EH existed ,which indicate that ADMA might be involved in the occurrence and development of EH .

Objective To study the correlation between the level of CaMKIV and essential hypertension (EH) in Shihezi community. Methods One hundred and forty-six patients with EH and 142 with normal blood pressure are enrolled from 15 communities in shihezi. We collected the clinical data, including blood pressure, body mass index, waist circumference, blood lipids. The serum level of CaMKIV was detected using an enzyme linked immunosorbent assay. Results The serum level of CaMKIV in the EH group was significantly lower than that in the normal blood pressure group (P < 0.05). The serum CaMKIV was negatively correlated with systolic BP and diastolic BP (r = -0.304, -0.452, all P < 0.05), with more obvious correlation with patients whose diastolic blood pressure was over 100 mmHg (r = -0.571, P < 0.05). Conclusions The serum level of CaMKIV is negatively correlated with EH, which is an independent factor of EH.

Objective To explore the relationship among the left ventricular rotation and twist, Tei index and left ventricular function in chronic heart failure patients and provide reliable indicator of chronic heart left ventricular myocardial function and mechanical movement. Methods Seventy-nine chronic heart failure patients with cardiac function classⅡ(32 cases), cardiac function classⅢ(26 cases) and cardiac function classⅣ(21 cases) and 28 healthy volunteer were included. All subjects underwent conventional echocardiography and two dimensional-speckle tracking imaging. The mitral annulus tissue Doppler spectrums at apical four chambers view, two-dimensional images of left ventricle at basal and apical level were acquired. The left ventricular twist, segmental rotation at short axis view and Tei index were measured. The differences were compared and the correlations were analyzed. Results (1) There were signiifcant differences for Tei index among the four group (χ2=88.31, P<0.01). The Tei index of healthy control group and chronic heart failure patients with cardiac function class Ⅱ , class Ⅲand class Ⅳwere 0.33±0.19, 0.37±0.18, 0.46±0.31 and 0.49±0.33. The Tei index gradually increased when the heart function decreased. (2) The left ventricular twist were also signiifcantly different among the four groups (F=25.99, P<0.01). The left ventricular twist of healthy control group and chronic heart failure patients with cardiac function classⅡ, classⅢ and classⅣwere (12.89±2.65)°, (12.29±1.94)°, (12.38±2.13)° and (8.46±2.90)°. The left ventricular twist gradually decreased when the heart function decreased. The differences between chronic heart failure patients with cardiac function classⅣand healthy control group, chronic heart failure patients with cardiac function classⅡand classⅢwere signiifcant (q=6.43, 5.71 and 4.17, all P<0.05). (3) The left ventricular segmental rotations at basal level were significantly different among healthy control group and chronic heart failure patients with cardiac function classⅡ,ⅢandⅣ(F=9.51, 9.47, 7.41, 10.27, 9.42 and 11.34, all P<0.01 ). The left ventricular segmental rotations were positively correlated with Tei index and the segmental rotation of anterior wall was most correlated with Tei index (r=0.327, 0.277, 0.266, 0.321, 0.306 and 0.325, all P<0.01). (4) The left ventricular segmental rotations at apical level were signiifcantly different among four groups (F=6.17, 3.49, 3.46, 3.50, 3.48 and 2.81, all P<0.01). The left ventricular segmental rotations were negatively correlated with Tei index and the segmental rotation of anterior wall was most correlated with Tei index (r=-0.362,-0.278,-0.251,-0.279,-0.290 and-0.288, all P<0.01). (5) The left ventricular twist and Tei index were negatively correlated (r=-0.443, P<0.01). Conclusions The left ventricular twist and segmental rotation at short axis view in patients with chronic heart failure decreased and Tei index gradually increased. The left ventricular twist and Tei index were negatively correlated. The combination of two-dimensional speckle tracking technology and Tei index could achieve noninvasive assessment of left ventricular mechanical movement and left heart function in chronic heart failure patients.

Objective To study the effects of broad-spectrum antibiotics, including the third generation Cephalosporin and Carbapenems, on intestinal enterococci in septic rats. Methods Ninety-one SD rats were randomly divided into normal control group, scald group, scald group with 3 days of ceftriaxone treatment, scald group with 9 days of ceftriaxone treatment, scald group with 3 days of imipenem treatment, scald group with 9 days of imipenem treatment, and sepsis group, sepsis group with 3 days of ceftriaxone treatment, sepsis group with 9 days of ceftriaxone treatment, and sepsis group with 3 days of imipenem treatment, sepsis group with 9 days of imipenem treatment. All the animal were subjected to 30% TBSA Ⅲ degree scald injury on their back, followed by endotoxin challenge with a dose of 20mg/kg 24 hours after the burn injury. The animals were treated with intraperitoneal injection of ceftriaxone (60mg/kg, q12h) or imipenem (60mg/kg, q12h) 24h after the second hit with endotoxin. At the end of the treatment, intestinal enterococci in colon were cultured. The number and variety of the bacteria were also determined. Results The number of enterococci in the gut of the septic rats was significantly increased after the second hit with endotoxin, exceeding that of the rats in normal control group and scald group(P

Objective To study the effects of broad-spectrum antibiotics, including the third generation Cephalosporin and Carbapenems, on intestinal commensal bacilli in rats with sepsis. Methods Ninety-one SD rats were randomly divided into normal control group, scald group, scald group with 3 days of ceftriaxone treatment, scald group with 9 days of ceftriaxone treatment, scald group with 3 days of imipenem treatment, scald group with 9 days of imipenem treatment, and sepsis group, sepsis group with 3 days of ceftriaxone treatment, sepsis group with 9 days of ceftriaxone treatment, and sepsis group with 3 days of imipenem treatment, sepsis group with 9 days of imipenem treatment. All the animal were subjected to 30% Ⅲdegree scald injury on their back, followed by endotoxin challenge with a dose of 20mg/kg 24 hours after the burn injury. The animals were treated with intraperitoneal injection of ceftriaxone (60mg/kg, q12h) or imipenem (60mg/kg, q12h) 24h after the second hit with endotoxin. At the end of the treatment, bacilli in the colon were cultured. The number and variety of the bacteria were also determined. Results The antibiotics obviously reduced the number of colibacilli(P