Objective To investigate the effect of ischemic preconditioning(IPC) on myocardial ischemic reperfusion injury(I/R) of elderly rats. Methods Fiftysix Wistar rats, of which there were 28 aged from 21-23months(elderly rat) and 28 aged from 4-5months(young rat), were used to build isolated heart perfusion Langendorff model. The rats were divided into 7 groups with random number table（8 in each group）: adult control group, adult I/R group, adult IPC group, elderly control group, elderly I/R group, elderly IPC group and elderly enhanced IPC group. The control group underwent a 90-min perfusion without any intervention; the I/R group underwent a 30-min equilibration period, then a 30-min ischemia and a 30-min reperfusion; the IPC group underwent a 10-min equilibration period, then a 5-min ischemia for twice and a 5-min reperfusion, after that a 30-min ischemia and [CM(158-3mm]a 30-min reperfusion; the enhanced IPC group underwent a 10-min equilibration period, then a 5-min ischemia for 4-times and a 5-min reperfusion, after that a 30-min ischemia and a 30-min reperfusion. The recovery rates of cardiac output(CO), left ventricular developed pressure (LVDP), the maximum rising and descending rate of left ventricular pressure (±dp/dtmax) after a 30-min reperfusion were compared among groups. The activity of creatine kinase (CK) in coronary outflow, the level of malonyldialdehyde (MDA) and superoxide dismutase (SOD) before ischemia and after a 30min reperfusion were detected. The myocardial infarction areas were compared among groups. Results After a 30min reperfusion, compared with adult I/R group, in adult IPC group CK reduced significantly(89.48±18.72 U/L vs. 115.76±16.72 U/L，q=6.061，Plt;0.01)，the level of MDA decreased significantly（9.53±3.44 nmol/ml vs. 16.84±2.29 nmol/ml，q=7.732，Plt;0.01)，the level of SOD increased significantly（584.7±122.62 U/ml vs. 429.46±85.24 U/ml，q=4.754，Plt;0.01)，the recovery rates of CO,LVDP,+dp/dtmax and -dp/dtmax increased ignificantly(78.69%±9.68% vs. 65.10%±8.63%，83.61%±8.46% vs. 67.23±8.68%，81.68±8.68% vs. 67.89%±6.89%，89.79%±7.78% vs. 66.79%±8.46%，Plt;0.01), the myocardial infarction areas reduced significantly (5.25%±4.33% vs. 14.75%±8.02%,q=7.458，Plt;0.01)。There was no statistical significance between elderly IPC group and elderly I/R group in the above indexes（Pgt;0.05）.However, There was statistical significances between elderly enhanced IPC group and I/R group. CK reduced significantly (88.60±28.32 U/L vs. 105.76±9.64 U/L，q=5.620，Plt;0.01)，the level of MDA decreased significantly（8.38±3.36 nmol/ml vs. 16.80±3.06 nmol/ml，q=7.500，Plt;0.01)，the level of SOD increased significantly（558.87±78.66 U/ml vs. 433.75±86.65 U/ml，q=7.335，Plt;0.01)，the recovery rates of CO,LVDP,+dp/dtmax and -dp/dtmax increased significantly (77.99%±10.02% vs. 66.26%±9.78%，85.59%±6.67% vs. 73.90%±6.66%，83.87%±9.98% vs. 68.90%±8.68%，86.01%±766% vs. 70.39%±7.98%，Plt;0.01)， the myocardial infarction areas reduced significantly (795%±6.32% vs. 1568%±10.36%,q=8.680， Plt;0.01). 〖WTHZ〗Conclusion The protective effect of IPC on I/R elderly rat hearts has weakened. The enhanced IPC is able to regain the protective effect of IPC on elderly rat hearts.
Objective To study the diagnostic and prognostic value of serum soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and cyclooxygenase-2 (COX-2) in abdominal infection-caused sepsis. Methods A total of 170 patients with abdominal infection treated in the First Hospital of Qinhuangdao between January 2019 and March 2022 were retrospectively selected and divided into sepsis group (n=76) and non-sepsis group (n=94) according to whether they were combined with abdominal infection-caused sepsis. In addition, 80 healthy people in the same period were selected as the control group. The levels of serum sTREM-1 and COX-2 in the three groups were detected and the differences were compared. The laboratory indexes, including white blood cell count, high-sensitivity C-reactive protein, and procalcitonin of patients with abdominal infection-caused sepsis were detected. The Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation System Ⅱ and prognosis (survival or death) of patients with abdominal infection-caused sepsis were evaluated. The correlations of serum sTREM-1 and COX-2 with the severity of sepsis were analyzed, and the diagnostic and prognostic value of sTREM-1 and COX-2 in abdominal infection-caused sepsis was assessed. Results The levels of serum sTREM-1 and COX-2 in the sepsis group were higher than those in the control group and the non-sepsis group (P<0.05). The levels of serum sTREM-1 and COX-2 in the sepsis group were positively correlated with white blood cell count, high-sensitivity C-reactive protein, procalcitonin, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation System Ⅱ score (P<0.05). The serum levels of sTREM-1 and COX-2 of patients who died during hospitalization in the sepsis group were higher than those of the surviving patients. The areas under the receiver operating characteristic curves of the serum sTREM-1 and COX-2 levels for diagnosing sepsis caused by abdominal infection were 0.814 [95% confidence interval (CI) (0.746, 0.882), P<0.001] and 0.848 [95%CI (0.788, 0.905), P<0.001], respectively, with critical values of 1.879 pg/mL and 18.75 ng/mL, respectively, and those for predicting the prognosis of patients with sepsis caused by abdominal infection were 0.775 [95%CI (0.659, 0.890), P<0.001] and 0.784 [95%CI (0.679, 0.889), P<0.001], respectively, with critical values of 2.283 pg/mL and 23.02 ng/mL, respectively (P<0.05). Conclusion The serum levels of sTREM-1 and COX-2 have certain value in the diagnosis and prognosis prediction of abdominal infection-caused sepsis.
Objective Isoflurane has an acute preconditioning effectiveness against ischemia in kidney, but this beneficial effectiveness can only last for 2-3 hours. To investigate whether isoflurane produces delayed preconditioningagainst renal ischemia/reperfusion (I/R) injury, and whether this process is mediated by hypoxia inducible factor 1α(HIF- 1α). Methods A total of 52 male C57BL/6 mice were randomly assigned to 4 groups (n=13 in each group): the controlgroup (group A), PBS/isoflurane treated group (group B), scrambled small interference RNA (siRNA)/isoflurane treated group (group C), and HIF-1α siRNA/isoflurane treated group (group D). In groups C and D, 1 mL RNase-free PBS containing 50 μg scrambled siRNA or HIF-1α siRNA was administered via tail vein 24 hours before gas exposure, respectively. Equivalent RNasefree PBS was given in groups A and B. Then the mice in groups B, C, and D were exposed to 1.5% isoflurne and 25%O2 for 2 hours; while the mice in group A received 25%O2 for 2 hours. After 24 hours, 5 mice in each group were sacrificed to assesse the expressions of HIF-1α and erythropoietin (EPO) in renal cortex by Western blot. Renal I/R injury was induced with bilateral renal pedicle occlusion for 25 minutes followed by 24 hours reperfusion on the other 8 mice. At the end of reperfusion, the serum creatinine (SCr), the blood urea nitrogen (BUN), and the histological grading were measured. Results The expressions of HIF-1α and EPO in groups B and C were significantly higher than those in group A (P lt; 0.01). The concentrations of SCr and BUN in groups B and C were significantly lower than those in group A, as well as the scores of tubules (P lt; 0.01), and the injury of kidney was amel iorated noticeably in groups B and C. The expressions of HIF-1α and the concentrations of SCr and BUN in group D were significantly lower than those in group A (P lt; 0.01). Compared with groups B and C, the expression of HIF- 1α and EPO in group D decreased markedly (P lt; 0.01), the concentrations of SCr and BUN were increased obviously, as well asthe scores of tubules (P lt; 0.01), and the renal injury was aggratived significantly. Conclusion Isoflurane produces delayed preconditioning against renal I/R injury, and this beneficial effectiveness may be mediated by HIF-1α.
Objective To determine the protection effects and mechanisms for immature myocardium with limbs ischemic preconditioning (LIP). Methods Using the Langendorff perfusion apparatus to perfuse isolated hearts, we randomly divided 30 Japanese longeared white rabbits into 5 groups, each having 6 rabbits. For the I/R group，after the perfusion model was established, the isolated hearts underwent 15 min of perfusion with KH solution before working for another 15 min . Then perfusion was stopped to cause ischemia for 45 min before reperfusion for 15 min and working for another 30 min . For E1 group, the model was established by 3×LIP (double limbs obstructed for 5 min followed by 5 min reperfusion for 3 times) and then procedures of the I/R group were carried out. For E2 group, before procedures of the E1group were done, superoxide dismutase (SOD) was injected till LIP was completed. For E3 group, intravenous protein kinase C (PKC) polymyxin (PMB) was injected for 10 minutes before E1 procedures were repeated. For E4 group, intravenous mitochondrial ATPsensitive K+ channels (mitoKATP) blocker 5-hydroxydecanoate was injected for 10 min before E1 procedures were carried out. The left ventricular function recovery, myocardial water content (MWC), creatine kinase (CK) and lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) and ATP content, SOD activity and superoxygen negative ion (O2 ·-) content were tested. Results Left ventricular recovery in E1 group was better than other groups (Plt;0.05). ATP content and SOD activity in E1 group were also better than all other groups (Plt;0.05). MWC in E1 group was lower than other groups (Plt;0.05). MDA content, CK and LDH leakage in E1 group were also lower than other groups (Plt;0.05). There was no significant difference of the above indications among I/R,E2,E3 and E4 groups, while the difference of O2·- content in E1,E3 and E4 groups before and after preconditioning was significant. Conclusion LIP has obvious protective effects for immature myocardium and the mechanisms are probably through PKC stimulation and opening of mitoKATP.
Objective To determine whether the different durations and times of the ischemic preconditioning affect the effectiveness of the ischemic preconditioning. Methods Ninety male Wistar rats were randomly divided into the control group and the eight preconditioned groups of 10 rats each. A transverse rectus abdominis musculocutaneous flap (TRAM) was elevated in each rat. The flaps were preconditioned by clamping the pedicle and reperfusing for 5 or 10 minutes per cycle. This was repeated for one or two cycles. The controls were simply perfused for 30 minutes. Each flap was then subjected to 4 hours of the global ischemia. Three rats in each group were killed for anestimate of the water content in the muscle and for observation on the muscularstructure under microscope. The flap surface survival areas of the other rats were calculated on the 7th postoperative day by the computerized video planimetry. Results The water content in the muscle was evidently reduced. The mean survival area of the flap in every preconditioned group increased by2-3 times compared with that of the controls(P＜0.001). The different proceduresof the ischemic preconditioning produced different protective effects. Conclusion The ischemic preconditioning is an available means to alleviate an ischemiareperfusion injury to the transverse rectus abdominis musculocutaneous flap in rats. The effect of the ischemic preconditioning is affected by the duration and time of the ischemic preconditioning.
ObjectiveTo systematically review the efficacy of remote ischemic preconditioning in myocardial protection for on-pump CABG patients. MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 1, 2015), WanFang Data, CBM and CNKI were searched from inception to January 2015 to collect randomized controlled trials (RCTs) about remote ischemic preconditioning on coronary artery bypass grafting under extracorporeal circulation. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was conducted using RevMan 5.2 software. ResultsA total of 11 RCTs involving 1 128 patients were included. The results of meta-analysis showed that, compared with patients in the control, the RIPC (remote ischemic preconditioning) patients had lower levels of troponin T (MD=-0.22, 95%CI -0.24 to -0.20, P < 0.000 01) and troponin I (MD=-1.91, 95%CI -2.43 to -1.38, P < 0.000 01). However, there were no statistical differences between the two groups in CK-MB, mortality at 30 days, inotropic support, length of stay in ICU or in hospital. ConclusionCurrent evidence indicates that RIPC myocardial protection has little impact on patients undergoing CABG surgery. Due to the quantity and quality limitations of included studies, more high quality studies are needed to verify the above conclusion.
Objective To investigate the protection on the intrahepatic cholangiocyte mediated by hypoxic preconditioning (HP) after liver transplantation and the role of vascular endothelial growth factor (VEGF). Methods The model of autologous liver transplantation was established, and the rats were divided into 3 groups: autologous liver transplantation group, hypoxic preconditioning before operation group (HP group) and sham operation group. At 6, 12, 24, 48 h after operation, blood samples were collected for examination of the serum total bilirubin (TBIL), direct bilirubin (DBIL) and alkaline phosphatase (ALP), and the expression of VEGF was detected by immunohistochemical method. The pathological changes of cholangiocytes were observed by light microscope. Results As compared with autologous liver transplantation group, the levels of seurm TBIL, DBIL and ALP in HP group were lower (P＜0.05), while the expression of VEGF in HP group was higher at the whole process (P＜0.05). The degrees of billiary epithelium damage and inflammatory infiltration in autologous liver transplantation group were more severe than those in HP group. Conclusion HP has protective effect on cholangiocytes after liver transplantation, in which VEGF may play an important role.
Abstract： Ischemia postconditioning is a new concept based on ischemic preconditioning. It has become a hot topic in protection of ischemic-reperfusion injury because of its effective protection, relative ease of application, and postconditioning. However, its precise mechanisms and most effective application methods are still unclear. This review covers recent progress in the understanding, developments (in remote postconditioning and pharmacological postconditioning), applications to the protection of heart, lung, liver, kidney, and brain, mechanisms and appropriate protocol of ischemic post-conditioning.
ObjectiveTo explore the conditions of synovial derived mesenchymal stem cells (SMSCs) differentiating into the fibrocartilage cells by using the orthogonal experiment. MethodsThe synovium was harvested from 5 adult New Zealand white rabbits, and SMSCs were separated by adherence method. The flow cytometry and multidirectional differentiation method were used to identify the SMSCs. The conditions were found from the preliminary experiment and literature review. The missing test was carried out to screen the conditions and then 12 conditions were used for the orthogonal experiment, including transforming growth factor β1 (TGF-β1), bone morphogenic protein 2 (BMP-2), dexamethasone (DEX), proline, ascorbic acid (ASA), pyruvic acid, insulin+transferrin+selenious acid pre-mixed solution (ITS), bovin serum albumin (BSA), basic fibroblast growth factor (bFGF), intermittent hydraulic pressure (IHP), bone morphogenic protein 7 (BMP-7), and insulin-like growth factor (IGF). The L60 (212) orthogonal experiment was designed using the SPSS 18.0 with 2 level conditions and the cells were induced to differentiate on the small intestinal submucosa (SIS)-3D scaffold. The CD151+/CD44+ cells were detected with the flow cytometry and then the differentiation rate was recorded. The immumohistochemical staining, cellular morphology, toluidine blue staining, and semi-quantitative RT-PCR examination for the gene expressions of sex determining region Y (SRY) -box 9 gene (Sox9), aggrecan gene (AGN), collagen type I gene (Col I), collagen type Ⅱ gene (Col Ⅱ), collagen type IX gene (Col IX) were used for result confirmation. The differentiation rate was calculated as the product of CD151/CD44+ cells and cells with Col I high expression. The grow curve was detected with the DNA abundance using the PicoGreen Assay. The visual observation and the variances analysis among the variable were used to evaluate the result of the orthogonal experiment, 1 level interaction was considered. The q-test and the least significant difference (LDS) were used for the variance analysis with a type Ⅲ calibration model. The test criteria (α) was 0.05. ResultsThe cells were certified as SMSCs, the double-time of the cells was 28 hours. During the differentiation into the fibrocartilage, the volume of the SIS-3D scaffold enlarged double every 5 days. The scaffolds were positively stained by toluidine blue at 14 days. The visual observation showed that high levels of TGF-β1 and BMP-7 were optimum for the differentiation, and BMP-7 showed the interaction with BMP-2. The conditions of DEX, ASA, ITS, transferrin, bFGF showed decreasing promotional function by degrees, and the model showed the perfect relevance. P value was 0.000 according to the variance analysis. The intercept analysis showed different independent variables brought about variant contribution; the TGF-β1, ASA, bFGF, IGF, and BMP-7 were more remarkable, which were similar to the visual observation. ConclusionIn the process of the SMSCs differentiation into the fibrocartilage, the concentrations of TGF-β1, ASA, bFGF, and IGF reasonably can improve the conversion rate of the fibrocartilage cells. The accurate conditions of the regulatory factor should be explored further.
The three-dimensional (3D) liver and tumor segmentation of liver computed tomography (CT) has very important clinical value for assisting doctors in diagnosis and prognosis. This paper proposes a tumor 3D conditional generation confrontation segmentation network (T3scGAN) based on conditional generation confrontation network (cGAN), and at the same time, a coarse-to-fine 3D automatic segmentation framework is used to accurately segment liver and tumor area. This paper uses 130 cases in the 2017 Liver and Tumor Segmentation Challenge (LiTS) public data set to train, verify and test the T3scGAN model. Finally, the average Dice coefficients of the validation set and test set segmented in the 3D liver regions were 0.963 and 0.961, respectively, while the average Dice coefficients of the validation set and test set segmented in the 3D tumor regions were 0.819 and 0.796, respectively. Experimental results show that the proposed T3scGAN model can effectively segment the 3D liver and its tumor regions, so it can better assist doctors in the accurate diagnosis and treatment of liver cancer.