Protective Effects of Different Doses of Human Umbilical Cord Mesenchymal Stem Cell on the Acute Lung Injury in Rats with Severe Burn / 现代生物医学进展

Objective:To investigate the protective effect of intratracheal transplantation of different dose of human umbilical cord mesenchymal stem cells (MSCs) in rats with acute lung injury induced by severe burns.Methods:Seventy-five male Wistar rats were randomly divided into five groups:Sham(group A),Saline group(group B) and different doses of hUMSCs transplantation groups(C,D and E).The dosage ofhUMSCs was 1 × 105,5 × 105 and 1 × 106 respectively.Rats inflicted by 50 ％TBSA Ⅲ degree scalding employed as the model.After modeling,rats in group B and transplantation groups were immediately fluid resuscitated.Transplantation groups were intratracheally administered different dose hUCMSCs (0.2 mL),and group B were given normal saline in the same dose intratracheally.The lung tissue samples were collected on day 1,day 3 and day 7 after administration.HE staining was used to observe the pathological changes of lung tissue.MPO and CD68 immunohistochemical staining were used to observe the positive expression of neutrophils and macrophages in lung tissue.Results:Lung pathology showed that alveolar cavity was clear,alveolar structure integrity,occasionally a small amount of inflammatory cells of group A at each time point.At 1 day after scald,group B and the transplantation group (group C,D,E)the alveolar septum was thickened,and there was visible pulmonary capillary hyperemia,as well as a large amount of inflammatory cell infiltrations in the pulmonary capillaries and alveolar space.At 3 day,group B and the transplantation group alveolar structural damage,pulmonary hemorrhage and inflammatory cell infiltrations were better than those in 1 day.Compared with group B,the alveolar structure was clear and the septum was thinner,but there was no significant difference between the transplantation groups.On the 7 day after scald,the lung injury in the transplanted group was significantly less than group B,and the recovery of the injured lung tissue in E group was the most obvious.The number of the MPO positive cells increased significantly on the first day after scald (P ＜0.05) compared with group A,but there was no significant difference between the two groups.Compared with B group,the number of positive cells in transplantation group was significantly reduced at 3 and 7 day after scald,(P＜0.05),and the number of positive cells in group E was significantly lower than other groups (P＜0.05).CD68 staining showed a significant increase in positive cells in each group on day 1 (P＞ 0.05).The number of positive cells decreased in 3 day after transplantation (P＜0.05),but there was no significant difference between the transplantation groups.The number of positive cells in transplantation group was significantly lower than group B (P＜0.05) after 7 day.Compared with group C and D,there was significant difference in group E (P＜0.05).Conclusions:Intratracheal transplantation of different dose hUCMSCs have protective on severe burns induced acute lung injury models;the protection mechanisms may be that the hUCMSCs transplantation can inhibit the invasion of the inflammatory cells in lung tissues,and the optimal dosage is 1 × 106.

Effects of Hypoxia / Reoxygenation on Myocardial Cells: Protected by Components of Water Extract from Qi-Xue Bing-Zhi Recipe / 世界科学技术-中医药现代化

This study was aimed to observe the protective effects of components of water extract from Qi-Xue Bing-Zhi recipe (CWQB) on myocardial cells from hypoxia/reoxygenation (H/R) injury,by optimizing the metabolism of highenergy phosphates and then preventing cell damage and early apoptosis correlatively.Myocardial cells were separated and extracted from newborn SD rats.And then,H/R models were made by depriving oxygen for 3 hours and then regaining for 2 hours.Cardiomyocytes were divided into four groups,which were the control (normal oxygen) group,H/R (H/R model) group,TMZ (H/R model + 100 μmol/L Trimetazidine,TMZ) group,and CWQB (H/R model + 1 mmol/L CWQB) group.High-performance liquid chromatography (HPLC) was used in the content determination of adenosine monophosphate (AMP),adenosine diphosphate (ADP),adenosine triphosphate (ATP) in each group for the calculation of total adenylic acid (TAN) and energy charge (EC).Enzyme linked immunosorbent assay (ELISA) was used in the detection of myocardial damage markers,such as creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT).The early apoptosis of myocardial cells were assessed by flow cytometry (FCM).The results showed that compared with H/R group,contents of AMP in the TMZ group and CWQB group were decreased,while contents of ADP,ATP,TAN and EC were all increased in both groups.The increasing degrees of ADP,ATP and TAN in TMZ group were higher than those of the CWQB group (P ＜ 0.05).Contents of CK-MB and cTnT were significantly decreased in the TMZ group and the CWQB group.Content of cTnT decreased more significantly in the CWQB group (P ＜ 0.05).In the TMZ group and the CWQB group,early apoptosis rate was decreased.The decreasing in the TH group was more significant (P ＜ 0.05).The correlation analysis showed that the level of CK-MB and concentration of ADP had significant negative correlation.The early apoptosis rate and AMP had significant positive correlation.The early apoptosis rate had negative correlation with concentrations of ADP and ATP (P ＜ 0.01).It was concluded that CWQB recipe can decrease the concentration of AMP in H/R cardiomyocytes,increase the concentrations of ADP,ATP,TAN and EC,and decrease myocardial damage makers such as CK-MB and cTnT,depress early apoptosis rate in H/R cardiomyocytes,in order to display its cardioprotective effects in H/R injury.

The early survival rate and its influencing factors of extremely premature and extremely low birth weight infants / 中国新生儿科杂志

Objective To study the early survival rate and its influencing factors of extremely preterm infants and extremely low birth weight ( ELBW ) infants.Method All extremely preterm infants and/or ELBW infants in Shandong Provincial Hospital from January , 2010 to December 2015 were studied retrospectively.The factors affecting their survival rate and their complications were analyzed retrospectively . All cases were assigned into the survival group and the death group .On the other hand , they were also assigned into two groups according to their birth , pre-2014 and post-2014.Result A total of 142 extremely preterm infants and/or ELBW infants were enrolled, their gestational age was 28 (27, 29) weeks, birth weight was 925 (830, 965) g.76 cases (53.5%) survived, 66 cases (46.5%) died.Factors associated with the survival rate were early onset sepsis , placental abruption , perinatal asphyxia , birth weight and pulmonary hemorrhage (P<0.05).There were 67 cases pre-2014 in which 30 cases survived (44.8%), while 75 cases post-2014 in which 46 cases survived ( 61.3%) .Comparative analysis between the two groups pre-2014 and post-2014 revealed that the survival rate was significantly different (χ2 =3.900, P=0.048).The top 2 underlying causes of death before 2014 were perinatal asphyxia and early onset sepsis . Furthermore, early onset infection became the first cause of death after 2014.Conclusion Along with the prevalence of neonatal resuscitation program and the optimization of respiratory support strategies in premature infants , the early survival rate of extremely preterm infants and /or ELBW infants has improved significantly.However, early onset sepsis may have been the crucial cause for their perinatal mortality .

Neuroprotection of Dexmedetomidine against Cerebral Ischemia-Reperfusion Injury in Rats: Involved in Inhibition of NF-κB and Inflammation Response

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

Neuroprotection of Dexmedetomidine against Cerebral Ischemia-Reperfusion Injury in Rats: Involved in Inhibition of NF-κB and Inflammation Response

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

Advances in the research of the role of mesenchymal stem cell in wound healing / 中华烧伤杂志

Wound healing is a dynamic and complicated process, which generally takes three overlapping phases: inflammation, proliferation, and remodeling. If wounds complicated by severe trauma, diabetes, vascular dysfunction disease, or a massive burn injury failed to pass through the three normal phases of healing, they might end up as chronic and refractory wounds. Mesenchymal stem cells (MSCs) play different important roles in the regulation of all the phases of wound healing. MSCs can be recruited into wound and differentiated into wound repair cells, as well as promote wound healing by exerting functions like anti-inflammation, anti-apoptosis, and neovascularization. This review focuses on the role and mechanism of MSCs in each phase of the wound healing process.

Effects of endotoxin/lipopolysaccharide on proliferation and apoptosis of human umbilical cord mesenchymal stem cells / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effects of different concentrations of lipopolysaccharide (LPS) on proliferation and apoptosis of human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro, and to explore their possible mechanism.</p><p><b>METHODS</b>hUCMSCs from umbilical cord tissue of full-term healthy fetus delivered by caesarean section were isolated and cultured in vitro using tissue attachment method. The 3rd passage hUCMSCs were used in the study. Cells were divided into groups A, B, C, D, and E, which were treated with DMEM/F12 medium containing 0, 0.1, 1.0, 10.0, and 100.0 µg/mL of LPS respectively. In groups B, C, D, and E, methyl-thiazole-tetrazolium assay was used to detect proliferative activity of hUCMSCs at post treatment hour (PTH) 12, 24, and 48 (denoted as absorption value), with 5 samples in each group at each time point; apoptosis of hUCMSCs at PBH 24 was identified with acridine orange-ethidium bromide (AO-EB) staining, with 4 samples in each group; apoptotic rate of hUCMSCs was determined by flow cytometer, with 5 samples in each group. Above-mentioned indexes were determined in group A at the same time points. Data were processed with analysis of variance and LSD- t test.</p><p><b>RESULTS</b>(1) There was no statistically significant difference in proliferative activity of hUCMSCs at PTH 12 among groups A, B, C, D, and E (with t values from -1.67 to 1.33, P values above 0.05). Compared with that of group A, proliferative activity of hUCMSCs was increased in groups B, C, and D at PTH 24 and 48 (with t values from -13.42 to 17.34, P < 0.05 or P < 0.01), especially so in group C. Proliferative activity of hUCMSCs was lower in group E at PTH 24 and 48 than in group A (with t values respectively 8.64 and 17.34, P values below 0.01). (2) Obvious apoptosis of hUCMSCs was observed in group E but not in the other 4 groups with AO-EB staining. (3) Apoptosis rates of hUCMSCs in groups A, B, C, D, and E were respectively (3.1 ± 0.6)%, (2.6 ± 0.7)%, (2.9 ± 0.8)%, (3.1 ± 0.4)%, (25.1 ± 2.7)% (F = 272.19, P < 0.01). Apoptotic rate of hUCMSCs in group B, C, or D was respectively close to that in group A (with t values respectively 1.22, 0.57, -0.14, P values above 0.05), but it was higher in group E than in group A (t = -17.63, P < 0.01).</p><p><b>CONCLUSIONS</b>hUCMSCs proliferation may be promoted by low concentration of LPS. hUCMSCs proliferation is inhibited or induced to apoptosis along with the increase in concentration of LPS, and it may be related to activation of different major molecular signaling pathways by different concentrations of LPS.</p>

Usefulness of nasal continuous positive airway pressure in acute congestive heart failure infants with pulmonary artery hypertension and congenital heart disease / 中华实用儿科临床杂志

Objective To describe the early use of nasal continuous positive airway pressure (nCPAP) ventilation for infants presenting acute congestive heart failure (CHF) complicated by congenital heart disease (CHD) and pulmonary artery hypertension (PH).Methods Sixty infants with CHD treated for acute CHF were randomly divided into the nCPAP group (n =32) and the non-nCPAP group (n =28).Data were analyzed,which included lactic acid value (Lac) by arterial blood gas analysis,calculation of oxygenation index [pa (O2)/FiO2],detection of serum N-terminal pro-brain natriuretic peptide of type B (NT-proBNP) level,determination of left ventricular end diastolic volume index (LVEDVI),left ventricular ejection fraction (LVEF) and pulmonary artery systolic pressure (PASP) by noninvasive bedside ultrasonic cardiogram (UCG).Results 1.Comparison of arterial blood gas between the 2 groups:1 d after treatment,there were significant differences in pa (O2)/FiO2 and Lac between the 2 groups (t =4.743,5.402,all P ＜ 0.05).A significant difference was found in the pa (O2)/FiO2 between the nCPAP group and the non-nCPAP group 3-7 d after treatment(t =6.366,P ＜ 0.05).The level of Lac had no significant difference between the 2 groups 3-7 d after treatment(t =1.812,P ＞ 0.05).2.Comparison of index of heart function between the 2 groups:after 3-7 d treatment,LVEDVI,LVEF,and PASP were statistically different between the 2 groups (t =2.052,2.704,2.019,all P ＜0.05).3.Comparison of serum indexes between the 2 groups:3-7 d after treatment,serum NT-proBNP level was improved dramatically compared with the non-nCPAP group(t =9.869,P ＜0.05).4.Comparison of clinical prognosis between the 2 groups:the differences in needing endobronchial intubation rate,mechanical ventilation time,time in PICU and mortality rate were all statistically significant between the 2 groups (x2 =5.505,P =0.019; t =4.788,P =0.000;t =5.068,P =0.000 ;x2 =4.284 ;P =0.038).Conclusions The early use of noninvasive nCPAP for eligible patients with acute CHF complicated by CHD and PH seems to improve their prognosis by improving pa (O2)/FiO2,reducing left ventricular and right ventricular afterload and improving the left ventricular function.

Role of oxLDL/LOX-1 system and NF-κB pathway in early diabetic vascular endothelial dysfunction / 中华内分泌代谢杂志

Diabetic rat model was established by peritoneal injection of streptozocin.At the end of 2 weeks,oxidized low-density lipoprotein (oxLDL) level in diabetic rats was raised [ ( 2.87 ± 0.40 vs 2.27 ± 0.36 ) μg/dl,P＜0.05 ] and endothelium-dependent relaxation was sluggish compared with normal rats.At the end of 6 weeks,oxLDL level continued to increase [ 4.32 ±0.66 ) μg/dl,P＜0.01] and endothelium-dependent maximum relaxation ( Rmax ) was decreased obviously ( P ＜0.01 ).Meanwhile,the protein and mRNA expressions of lectin-like oxidized lowdensity lipoprotein receptor-1 ( LOX-1 ),NF-kB,and ICAM-1 on vessel wall of diabetic rats were higher than those in normal rats,and LOX-1 mRNA was positively correlated with the levels of oxLDL,NF-kB,and ICAM-1 mRNA,while negatively correlated with Rmax,indicating that OxLDL/LOX-1 system may cause early endothelial dysfunction in diabetes via activating NF-kB and up-regulating ICAM-1 expression.

Clinical significance of dynamic hypoalbuminemia monitoring in children with severe sepsis / 中国小儿急救医学

Objective To study serum albumin levels in children with severe sepsis and to correlate serum albumin levels with patient outcome and to identify the causes inducing hypoalbuminemia and its effective countermeasures.Methods Seventy-five children admitted to PICU of Provincial Hospital Affiliated to Shandong University for severe sepsis were included in the study from Aug 2010 to Sep 2011.According to their serum albumin levels within 24 hours and on the third and the seventh day of admission to PICU,75 children were divided into hypoalbuminemia group and normal serum albumin group.Then hypoalbuminemia group was divided into instant hypoalbuminemia group and continuous hypoalbuminemia group according to the duration of hypoalbuminemia.The correlation between the occurring and duration of hypoalbuminemia with patients' prognosis,the etiopathogenisis of hypoalbuminemia and its effective countermeasures were analyzed.Results (1) Sixty-three cases (84.0％) proceeded hypoalbuminemia and their mortality was 33.3％ (21/63),while 12 cases (16.0％) showed normal serum albumin level and their mortality was 0.(2) In 63 patients with hypoalbuminemia,26 cases showed continuous hypoalbuminemia and their mortality was 46.0％,while 37 cases proceeded instant hypoalbuminemia and their mortality was 15.4％.There was significant difference (x2 =5.116,P ＜ 0.05) between their mortality.(3) In the 63 cases with hypoalbuminemia,32 cases presented with hepatic injury and their mortality was 37.5％,13 cases proceeded capillary leakage and their mortality was 23.1％,and 18 cases displayed hepatic injury complicated with capillary leakage and their mortality was 33.3％.There was significant difference (x2 =7.812,P ＜ 0.05) between the mortality with different causes.Conclusion Hypoalbuminemia influenced the prognosis of children with severe sepsis,the longer duration correlated with the worse prognosis.Hepatic injury and capillary leakage were two main causes inducing hypoalbuminemia.Active treatment of hypoproteinemia aimed directly at different causes could improve their prognosis significantly.