Application of a novel artificial perfusate based on oxygen-carrying nanoparticles in normothermic machine perfusion for porcine liver preservation after cardiac death / 浙江大学学报·医学版

OBJECTIVE@#To investigate the efficacy of a novel artificial perfusate based on oxygen-carrying perfluoronaphthalene-albumin nanoparticles in normothermic machine perfusion (NMP) for preservation of porcine liver donation after cardiac death.@*METHODS@#Artificial perfusate with perfluoronaphthalene-albumin nanoparticles was prepared at 5% albumin (w/v) and its oxygen carrying capacity was calculated. The livers of 16 Landrace pigs were isolated after 1 h of warm ischemia, and then they were divided into 4 groups and preserved continuously for 24 h with different preservation methods: cold preservation with UW solution (SCS group), NMP preservation by whole blood (blood NMP group), NMP preservation by artificial perfusate without nanoparticles (non-nanoparticles NMP group) and NMP preservation by artificial perfusate containing nanoparticles (nanoparticles NMP group). Hemodynamics, tissue metabolism, biochemical indices of perfusate and bile were monitored every 4 h after the beginning of NMP. Liver tissue samples were collected for histological examination (HE and TUNEL staining) before preservation, 12 h and 24 h after preservation.@*RESULTS@#The oxygen carrying capacity of nanoparticles in 100 mL artificial perfusate was 6.94 μL/mmHg (1 mmHg=0.133 kPa). The hepatic artery and portal vein resistance of nanoparticles NMP group and blood NMP group remained stable during perfusion, and the vascular resistance of nanoparticles NMP group was lower than that of blood NMP group. The concentration of lactic acid in the perfusate decreased to the normal range within 8 h in both nanoparticles NMP group and blood NMP group. There were no significant differences in accumulated bile production, alanine aminotransferase and aspartate aminotransferase in perfusate between nanoparticles NMP group and blood NMP group (all P>0.05). After 24 h perfusion, the histological Suzuki score in blood NMP group and nanoparticles NMP group was lower than that in SCS group and non-nanoparticles NMP group (all P<0.05), and the quantities of TUNEL staining positive cells in blood NMP group and non-nanoparticles NMP group was higher than those in nanoparticles NMP group and SCS group 12 h and 24 h after preservation (all P<0.05).@*CONCLUSION@#Artificial perfusate based on oxygen-carrying nanoparticles can meet the oxygen supply requirements of porcine livers donation after cardiac death during NMP preservation, and it may has superiorities in improving tissue microcirculation and alleviating ischemia-reperfusion injury.

Analysis of risk factors of polymyxin B-associated acute kidney injury in intensive care unit patients with severe infection / 中华危重病急救医学

Objective:To investigate the incidence and risk factors of polymyxin B-associated acute kidney injury (AKI) in patients with severe infections caused by extensive drug resistance Gram negative bacteria (XDR-GNB)in intensive care unit (ICU).Methods:A retrospective study of adult patients with severe infection who received polymyxin B for more than 3 days in the department of critical care medicine of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from April 1st 2018 to January 31st 2020 were performed. AKI was diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The baseline data, indicators during treatment period and prognostic factors were compared between AKI group and non-AKI group. Factors with statistically significant difference in univariate analysis and important clinical factors were included in the Logistic regression model to analyze the risk factors of AKI.Results:Seventy-two patients were treated with polymyxin B for more than 3 days. Forty-nine patients were finally enrolled, with 32 patients developing polymyxin B-associated AKI, and the incidence was 44.4%. The baseline data was balanced in AKI group and non-AKI group, and there was no significant difference in the prognosis [death or discharge without medial order (cases): 14 vs. 6, discharged for improvement (cases): 18 vs. 11, χ 2 = 0.329, P = 0.566]. Polymyxin B-associated AKI occurred from 1 day to 14 days after treatment, with an average of (6.8±3.8) days. Among the 32 AKI patients, 2 cases were lost to follow up after discharge, while renal function recovered in 18 cases and unrecovered in 12 cases. The prognosis of patients without recovery of renal function was significantly worse than that of patients with renal function recovery [death or discharge without medial order (cases): 12 vs. 2, discharged for improvement (cases): 0 vs. 16, P = 0.000]. Single factor analysis showed that daily dosage of polymyxin B in AKI group was higher than that in non-AKI group (mg: 151.6±23.7 vs. 132.4±30.3), numbers of patients with daily polymyxin B dose ≥ 150 mg, using vasoactive drugs, or severe hypoalbuminemia (albumin≤25 g/L) were higher than those in non-AKI group (cases: 29 vs. 10, 18 vs. 4, 9 vs. 0), with statistically significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that daily dosage of polymyxin B ≥ 150 mg and use of vasoactive drugs were independent risk factors for polymyxin B-associated AKI [odds ratio ( OR) = 37.466, 95% confidence interval (95% CI) was 2.676-524.586, P = 0.007; OR = 22.960, 95% CI was 1.710-308.235, P = 0.018]. Conclusions:Comparing with non-AKI patients, more patients with polymyxin B-associated AKI had severe hypoalbuminemia, and the probability of using vasoactive drugs and the daily dose of polymyxin B were higher than non-AKI patients. Daily dose of polymyxin B ≥ 150 mg and using vasoactive drugs were independent risk factors for polymyxin B-associated AKI.

Inhibition of mouse Lewis lung cancer via intravenous administration of recombinant mouse sFlt1 adenovirus / 中国肺癌杂志

<p><b>BACKGROUND</b>It has been known that the growth of solid tumors is dependent on angiogenesis, and neoangiogeneses of tumor become main target to control tumor growth. The aims of this study are to investigate the inhibition effect of replicate-deficient adenovirus encoding the soluble form of mouse vascular endothelial growth factor receptor 1 (sFlt1-Adv) on angiogenesis and tumor growth in established tumor model.</p><p><b>METHODS</b>Mouse Lewis lung cancer cells were inoculated subcutaneously into C57 mice. sFlt1-Adv, GFP-Adv and normal saline were injected twice intravenously after establishing Lewis cancer model. Diameters of tumors were measured every other day. Tumors were resected, weighed and fixed in 3% paraformadehyde. Microvessel density of tumors was determined by immunohistochemical staining with anti-CD31 antibody.</p><p><b>RESULTS</b>The planted tumor volume and weight in sFlt1-Adv group were significantly lower compared with the two controls (P < 0.01). Its inhibition rate was 71.8%. The microvessel density in sFlt1-Adv group decreased markedly compared with that of the control groups (P < 0.01).</p><p><b>CONCLUSIONS</b>sFlt1-Adv can inhibit the growth of tumor through the inhibition of tumor angiogenesis. sFlt1-Adv may be potentially valuable for clinical treatment of solid tumor.</p>

Effects of extracellular signal-regulated kinase (ERK) on focal cerebral ischemia / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To determine the role of extracellular signal-regulated kinase (ERK)1/2 during focal cerebral ischemia.</p><p><b>METHODS</b>Left middle cerebral artery occlusion (MCAO) was undergone after the introduction of a nylon suture to the left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation was detected using Western blot analysis, and the morphological feature was determined by immunohistochemistry. An ERK pathway inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126), was administered intravenously 20 minutes before MCAO, and the neurological deficit levels and the infarct volumes were measured 24 hours after MCAO.</p><p><b>RESULTS</b>Phosphorylated ERK 1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours. The immunohistochemical study displayed a large number of pERK 1/2 positive cells in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126 treated mice which had undergone 24 hours of MCAO, the neurological deficit levels and the infarct volumes were 44.6% and 45.8% respectively, less than those of the control mice.</p><p><b>CONCLUSIONS</b>ERK plays an important role in focal cerebral ischemia and inhibition of the ERK pathway can help protect against ischemic brain injury, which may provide a therapeutic approach for cerebral ischemia.</p>

Relationship between plasma carbon monoxide and blood-brain barrier permeability in cirrhotic rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the relationship between plasma levels of carbon monoxide and blood-brain permeability in cirrhotic rats.</p><p><b>METHODS</b>We measured mean arterial pressure (MAP), heart rate, plasma levels of carbon monoxide and amount of Evans blue in the brain tissue taken as the index of blood-brain permeability in cirrhotic rats (n=10) and controls (n=10).</p><p><b>RESULTS</b>Cirrhotic rats showed significant increases in plasma carbon monoxide and amount of Evans blue in brain tissue compared with controls [(18.37 +/- 1.79) micromol/L,(18.52 +.- 1.39) ng/mg vs (10.27 +/- 1.21) micromol/L, (15.08 +/- 1.06) ng/mg; P< 0.01]. Carbon monoxide levels in cirrhotic rats correlated positively with blood-brain barrier permeability and inversely with MAP (r=0.72, P< 0.01; r= -0.67, P< 0.05).</p><p><b>CONCLUSIONS</b>Carbon monoxide, involving in the occurrence of hypotension and the increase of blood-brain barrier permeability, may play a role in the development of hepatic encephalopathy.</p>

Advances in the study of tumor suppressor genes in gliomas / 中国癌症杂志

Glioma is the most malignant tumor in CNS， the effect of present therapy is poor. A important discovery in tumor molecular biology is that the activation of oncogene and inactivation of tumor suppressor gene play an important role in the mechanism of tumorgenesis. The advances in the study of tumor suppressor genes in gliomas were reviewed.

Effect of endogenous carbon monoxide on intracellular calcium concentration in focal ischemic cerebral tissue in rats / 中国病理生理杂志

AIM: To study effect of endogenous carbon monoxide on intracellular calcium concentration and explore the mechanism in brain protection of endogenous CO in focal cerebral ischemia in rats. METHODS: SD rats were divided into three groups randomly, which including hemin, ZnPP group and saline group as control. Respectively saline, hemin, ZnPP were injected intra-peritoneally twelve hours before middle cerebral artery was occluded. Twenty four hours after MCAO model was set up, the concentration of carbon monoxide in blood and intracellular calcium in neural cells was examined. RESULTS: Contrast to saline group, the concentration of CO in blood rose up while intracellular calcium in occluded side decreased in hemin group; the concentration of CO in blood went down while intracellular calcium in occluded side rose up in ZnPP group, there was significant difference among them (P0.05). CONCLUSIONS: It may be one of mechanisms on brain protection in ischemic cerebral tissue that carbon monoxide affected intracellular calcium concentration of neural cells by regulating Ca~(2+)-K~+ channel on cell membrane as a messenger gaseous molecular and neurotransmitter. [

Effect of carbon monoxide on permeability of brain blood barrier in cerebral local ischemia rats / 中国病理生理杂志

AIM: To evaluate the effect of carbon monoxide(CO) on the permeability of brain blood barrier(BBB) in cerebral ischemic rats. METHODS: SD rats were divided into three groups. Saline, hemin or ZnPP were injected intraperitoneally 12 h before middle cerebral artery occlusion (MCAO), respectively. The concentration of blood CO and the permeability of BBB at 24 h after MCAO were measured. RESULTS: The CO concentration in blood in hemin group was higher than that in saline group( P 0.05). CONCLUSION: CO reduced the permeability of BBB as a messenger gas molecular when its intrinsic concentration was elevated.