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Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.

Dual-phase steels of 09CuPCrNi are prepared through intercritical quenching process. The influences of dual-phase treatment on the corrosion resistant property of the steels have been studied by electrochemical potentiodynamic tests and artificial salt spray tests. The results indicate that the corrosion behavior of DP780 and the as-received weathering steel in 5% sodium hydroxide, 3.5% sodium chloride, 5% sulphuric acid and various concentrations of hydrochloric acid solutions are identical, but dual-phase steels show least corrosion current as compared to the as-received steel. Rust layers of the as-received steel and DP780 are identical mainly consisting of three iron (hydr) oxides, goethite, akaganeite and lepidocrocite, and magnetite. Both the relative amount and morphology of phase constituents affect on the corrosion behavior of DP steels.

Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM(27-52), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from pro-adrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM(27-52). The rat vascular calcific model was replicated with vitamin D3 and nicotine. ADM or/and ADM(27-52) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P0.01), did not effect on calcium content (P0.05), reduced 44.4% calcium uptake (P0.01), lowered 21.1% alkaline phosphatase activity (P0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P0.01) in the aorta of rats with vascular calcification. ADM(27-52) receded 32.0% vascular calcific nodules (P0.01), taken from 55.5% calcium content (P0.01), did not affect calcium uptake (P0.05), inhibited 22.5% alkaline phosphatase activity (P0.01), and restrained 21.9% osteopontin-mRNA expression (P0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM(27-52) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM(27-52) in taking from calcium content (17.5%, P0.01) and in receding vascular calcific nodules (18.6%, P0.01). ADM could obviously enhance the action of ADM(27-52) in inhibiting alkaline phosphatase activity (14.4%, P0.01) and in reducing calcium uptake (11.4%, P0.01). ADM(27-52) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%, P0.01). It is concluded that ADM(27-52) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule.

In this study, we employed rat model of acute myocardial necrosis induced by isoproterenol (ISO) to study the possible roles of corin, the protease uniquely distributing in myocardium to convert pro-brain natriuretic peptide (proBNP) to BNP, and neutral endopeptidase (NEP), the major enzyme to degrade BNP, in changing the levels of BNP. In rats with isoproterenol alone, the myocardium necrosis occurred and the cardiac function was inhibited; the BNP contents in plasma and myocardium were upregulated, so did the myocardial corin mRNA level; the NEP activity in plasma and myocardium were downregulated. Omapatrilat (OMA) treatment relieved myocardial lesions and improved cardiac function. In the plasma and myocardium, omapatrilat treatment increased BNP contents, reduced NEP activity; in myocardium, mRNA level of proBNP and corin decreased, but NEP mRNA expression increased. Our study confirmed that omapatrilat treated myocardial necrosis effectively and suggested that increased BNP in rats with myocardial necrosis could depend on increased production and conversion as well as decreased degradation.

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

The dynamics of three-variable models of bursting are studied. It is shown that under certain conditions, the dynamics on the attractor can be essentially reduced to two dimensions. The salient dynamics on the attractor can thus be completely described by the return map of a section which is a logistic interval map. Two specific bursting models from the literature are shown to fit in the general framework which is developed. Bifurcation of the full system for one case in investigated and the dynamical behavior on the attractor is shown to depend on the position of a certain nullcline.

To observe the effect of salvianolic acid B (SalB) on high energy phosphate and activity of ATPase of cerebral ischemia in mice, and to study the role of SalB on hydrocephalus further.NIH mice were divided into four groups randomly: Sham-operated group, cerebral ischemia group, SalB-treated group and Nimodipine (Nim)-collated group. In Sal B-treated group, mice were injected with SalB (22.5 mg x kg(-1)) in vena caudalis at 30 min before the experiment. In Nim-collated group, Nim (0.03 mg x kg(-1)) was injected into tail vein at the same time, while the mice in Sham-operated group and cerebral ischemia group were injected the same volume normal saline. The acute cerebral ischemia model was established by ligating bilateral common carotid arteries for 30 min in mice, then the mice were killed and the content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (PCr) were observed, and the cerebral energy charge (EC) was computed. At the same time, activity of Na(+) -K(+) -ATPase and Ca2(+) -ATPase, content of water in brain tissue were measured.Compared with cerebral ischemia group, EC and content of ATP, ADP, PCr in SalB-treated group heightened evidently (P0.01). Moreover, activity of Na(+)-K+ ATPase and Ca2+ ATPase in SalB-treated group had a remarkable increase (P0.01). But the content of water in brain tissue decreased markedly (P0.05).The mechanism that SalB can relieve content of water in brain tissue of cerebral ischemia in mice, may be associated with improving the content of high-energy phosphoric acid compounds and enhancing the activity of ATPase.

To research the mechanism of Danzhi-xiaoyao San (DZXYS) for treating Alzheimer's disease model of rats dealt with D-galactose.An Alzheimer's disease-like model of rats has been set up with sc. D-galactose 150.0 mg kg-1 D-1 x 49 d. Comparing with Acricept in 0.54 mg kg-1 D-1 dosage as a positive control drug, DZXYS in 12.636 g kg-1 D-1 x 49 d dosage has orally been administrated orally to treat the injury in the Alzheimer's disease-like model of rats. The energy charge in the cerebral tissues had been detested with waters liquid chromatography; the protein content and DNA content in the cerebral tissues had been detested with ultraviolet assay, the relative content of aldose reductase-mRNA is detested with RT-PCR. The difference was analyzed between the control rats without D-galactose, the model rats dealt with D-galactose, the model rats treated with Aricept and the model rats treated with DZXYS, it is significant as P0.05.1) DZXYS can not affect the energy charge in their cerebral tissues. 2) DZXYS can increase the protein content from 0.3139 +/- 0.019468 to 0.3213 +/- 0.015528 (ni=10, P0.05) in their cerebral tissues. 3) DZXYS can increase the total DNA content from 1.093 +/- 0.267 to 1.488 +/- 0.341 (ni=10, P0.01) in their cerebral tissues. 4) DZXYS can increase the content of AR-mRNA in their cerebral tissue from 0.732 +/- 0.159 to 1.418 +/- 0.277 (ni=5, P0.01).It suggests that DZXYS could be effective in human Alzheimer's disease for its stabling gene expression, maintaining protein characteristics, recovering signal transduction in the Alzheimer's disease-like model rats dealt with D-galactose.

Previous studies have shown that mitochondrial coupling factor 6 (CF6) is an endogenous peptide that inhibits prostacyclin (PGI2) synthesis in vascular endothelial cells. In this study, we measured the plasma CF6 level of patients with acute myocardial infarction (AMI) to observe dynamic changes of CF6. All patients showed elevated plasma CF6 levels upon admission for treatment of AMI. Their CF6 levels peaked approximately 72 h after the onset of AMI and remained high for 7 days. At 7 days, their CF6 levels decreased to the level seen upon admission, but not to within a normal range. Hyperlipidemic patients had significantly greater CF6 levels at 24 h after onset of AMI than patients with a normal lipid profile. On admission, the plasma CF6 level in patients with a cardiac function of Killip class ≥II was higher than that in patients with a Killip class I cardiac function. At 3 days after the onset of AMI, the plasma CF6 levels of patients with a creatinine kinase (CK) peak value ≥1,500 units/l were significantly higher than those of patients with a CK peak value

Adrenomedullin (ADM) is a multifunctional peptide with important roles in the cardiovascular system, especially in the adjustment of cardiovascular and renal homeostasis. ADM is present in plasma, organs and tissues, and its activity increases during hypertension. It remains unknown whether the clearance of this peptide is altered during hypertension. Neutral endopeptidase (NEP) is the major enzyme in ADM's degradation. We observed the activity and distribution of NEP and the expression of its mRNA in the plasma, cardiac ventricle, aorta, jejunum and kidney of spontaneously hypertensive rats (SHRs) in order to study the possible role of NEP in elevating tissue ADM concentrations during hypertension. ADM and NEP were diffuse in all tissues studied. The level of tissue ADM was generally higher in SHR tissues than in control tissues, except in the renal medulla, and its mRNA expression was higher in all tissues. Plasma NEP activity, general NEP activity and the expression of NEP mRNA in the left ventricle, aorta and jejunum in SHRs was lower than that of controls, and the level of ADM was inversely correlated with NEP activity. NEP activity and mRNA and protein expression in SHR kidneys were higher than in control kidneys; moreover, the ADM content was positively correlated with NEP activity in the renal cortex. NEP activity in the lung of SHRs did not differ from that of controls. Thus, in SHRs, the local concentration and action of ADM in the tissues may be differentially regulated by NEP.

Adrenomedullin (ADM), a multifunction peptide with important roles in regulating cardiovascular homeostasis, has the vasodilatory properties and is of particular interest in the pathophysiology of sepsis. ADM levels in plasma and tissues are regulated by the proteolysis of neutral endopeptidase (NEP), the major enzyme of ADM degradation. We observed the NEP activity in the plasma, the activity and distribution of NEP and its mRNA expression in the tissues of rats in septic shock to study the possible role of NEP in elevating tissue ADM concentration during sepsis. ADM level increases progressively during sepsis except in the jejunum. Rats in early phase of shock (ES) showed diverse changes in tissue NEP activity. Plasma NEP activity, tissue NEP activity and its protein and mRNA expression in the left ventricle, aorta, jejunum and lung in the late phase of shock (LS) rats were lower than those in ES and the control, but no statistical change of NEP activity in the kidney was observed. The level of ADM was inversely correlated with NEP activity in the plasma, ventricle and aorta and positively correlated with NEP activity in the jejunum. Thus, in sepsis, the local concentration and action of ADM in tissues may be differentially regulated by NEP.

To establish a method for the determination of gossypol in cotton root bark.Samples were extracted with acetone, and determined on a C18 column with the mobile phase (Acetonitrile-0.2% phosphoric acid, 85:15) and UV-235 nm detector.The recovery rate was 97.6%, RSD 1.59% (n = 5).This method can be used for the determination of gossypol in cotton root bark and the content of gossypol in three different species has been determined.

AIM: To confirm the therapeutic effect of Zijin capsule on liver fibrosis in rat model. METHODS: Model group: Bovine serum albumin (BSA) Freund’s incomplete adjuvant 0.5 mL was injected subdermally at d1 d15 d22 d29 and d36 for primary sensitization. Seven days after the fifth injection, BSA antibody in the serum was detected by double agar diffusion method. Normal saline of 0.4 mL was injected through cauda vein to BSA antibody-positive rat twice a week for fifteen times. Traditional Chinese medicine (TCM) decoction group and Zijin capsule group: In the attack injection period, Chinese medicinal decoction or Zijin capsule was given ig, the others were the same as in the model group. NS was used in the control group. The collagen content of rat liver was determined by Bergman’s method and expressed as x- ± s. The liver pathological changes were divided into four grades and expressed as the avarage of the total rank sum. RESULTS: The collagen content (mg/g) of the liver in the control group (7.2 ± 1.9) was significantly lower than that in the other groups; it was higher in the model group (31.7 ± 16.6) than that in the two therapeutic groups; and lower in Zijin capsule group (9.7 ± 2.8) than that in the TCM decoction group (11.5 ± 5.3). The pathological changes were more aggravated in the model group (37.4) than those in the two therapeutic groups; and more severe in the TCM decoction group (30.2) than in the Zijin capsule group (22.9). CONCLUSION: The therapeutic effect of Zijin capsule on the model was confirmed.

AIM: To develop a pharmacodynamic model of portal hypertension from chronic hepatitis. METHODS: Pathological changes and collagen depositions were analyzed using morphometry to confirm CCl4-induced chronic hepatitis. At d0, d28, d56 and d84 of the process, the portal perfused velocities (μL/min) in isolated rat livers were exactly controlled with a quantified pump. The pressure (mmHg) was monitored with a Physiological System. The geometric concentrations of phenylephrine or acetylcholine were added to a fixed volume (300 mL) of the circulating perfusate. The equation, the median effective concentration and its 95% confidence intervals of phenylephrine or acetylcholine were regressed with Prism-4 software in non-linear fit and various slopes. In the isolated perfused rat livers with chronic hepatitis, both median effective concentrations were defined as the pharmacodynamic model of portal hypertension. RESULTS: At d0, d28, d56 and d84, the equations of portal pressure potency from the concentrations of phenylephrine used to constrict the portal vein in isolated perfused rat livers were Y = 0.1732 + 0.3970/[1 + 10(-4.3061-0.4407 X)], Y = -0.004934 + 0.12113/[1 + 10(-3.1247-0.3262 X)], Y = 0.0104 + 0.2643/[1 + 10(-8.8462-0.9579 X)], and Y = 0.01603 + 0.12107/[1 + 10(-5.1134-0.563 X)]; the median effective concentrations were 1.69 × 10-10 mol/L, 2.64 × 10-10 mol/L, 5.82 × 10-10 mol/L, and 8.24 × 10-10 mol/L, respectively. The equations from the concentrations of acetylcholine used to relax the portal vein were Y = -0.4548 + 0.3274/[1 + 10(6.1538 + 0.5554 X)], Y = -0.05391 + 0.06424/[1 + 10(3.8541 + 0.3469 X)], Y = -0.2733 + 0.22978/[1 + 10(3.0472 + 0.3008 X)], and Y = -0.0559 + 0.053178/[1 + 10(5.6336 + 0.5883 X)]; the median effective concentrations were 8.40 × 10-10 mol/L, 7.73 × 10-12 mol/L, 5.98 × 10-11 mol/L, and 2.66 × 10-10 mol/L, respectively. CONCLUSION: A pharmacodynamic model of portal hypertension in isolated perfused rat livers with chronic hepatitis was defined as the median effective concentrations of phenylephrine and acetylcholine.

In this paper, we give in Theorem 1 a characterization, based on graph theory, of when anM-matrixA admits anLU factorization intoM-matrices, whereL is a nonsingular lower triangularM-matrix andU is an upper triangularM-matrix. This result generalizes earlier factorization results of Fiedler and Ptak (1962) and Kuo (1977). As a consequence of Theorem 1, we show in Theorem 3 that the conditionx T A?0 T for somex>0, for anM-matrixA, is both necessary and sufficient forPAP T to admit such anLU factorization for everyn×n permutation matrixP. This latter result extends recent work of Funderlic and Plemmons (1981). Finally, Theorem 1 is extended in Theorem 5 to give a characterization, similarly based on graph theory, of when anM-matrixA admits anLU factorization intoM-matrices.