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The influence of the evolution rule of basicity (0.6∼2.4) on the mineral composition and microstructure of sinter is studied by using a polarizing microscope, and the comprehensive application analysis of the drum index, vertical sintering speed, and yield of sinter shows that, over the course of an increase in basicity (0.6∼1.0), the mineral structure changed from the original porphyritic-granular structure to a porphyritic structure. At the same time, there was no calcium ferrite phase in the bonding phase at a basicity of less than 1.0; therefore, the downward trend of the three indicators is obvious. When the basicity was further increased to approximately 1.6, the main structure of the mineral phase changed from a corrosion structure to an interweaving corrosion structure. Because of the existence of a porphyritic-granular structure, the structure of the mineral phase was extremely inhomogeneous and most complex near the basicity of 1.6; although a small amount of calcium ferrite displayed an acicular structure, the drum index appeared to show a very low value. With an increase in basicity to 2.0, the mineral phase structure was dominated by an interweaving corrosion structure with a uniform framework, and the content of calcium ferrite reached the highest value. Moreover, a clear acicular structure developed, and the drum index also increased to the highest value. At a basicity of more than 2.0, a mineral structure began to appear and the corrosion, porphyritic-granular structure, and the drum index also showed a slightly declining trend. Therefore, in the actual production process, basicity should be avoided as far as possible at around 1.0 and 1.6 and it should be controlled at around 2.0. At the same time, based on the mineral facies data set of this paper, the convolutional neural network is used to carry out a simple prediction model experiment on the basicity corresponding to the mineral facies photos, and the effect is quite good, which provides a new idea and method for the follow-up study of mineral facies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Jian-Ming Zhi et al.)

Autophagy affects the development, progression, and prognosis of various cancers including pancreatic cancer. To develop an autophagy-related prognostic model of pancreatic cancer, we systematically analyzed gene expression profile from The Cancer Genome Atlas and Genotype-Tissue Expression. Ten autophagy-relevant genes with potential prognostic values were identified, based on which a prognostic model was constructed. We divided patients into a high- and a low-risk group with this model. Time-dependent receiver operating characteristic and Kaplan-Meier curves were conducted to evaluate the accuracy of the model. The Area Under Curvevalues of this model at 12, 18, and 24 months were 0.76, 0.73, and 0.78, respectively. The model was further validated in two Gene Expression Omnibus datasets. Gene set enrichment analysis and Cibersort were applied to analyze immune infiltration patterns and immune checkpoint blockade (ICB) molecules. The expression of ICB molecules, such as PD-L1 and PD1 , presented significant correlation with the risk score. In conclusion, the risk score model established herein has been proved to be robust for evaluating the prognosis of pancreatic cancer and facilitate to improve the efficacy of ICB.

Focal adhesion kinase (FAK) is known to promote the proliferation, migration and survival of synovial cells and plays an important role in the occurrence, development and pathological process of rheumatoid arthritis (RA). The aim of the present study was to observe FAK changes in synovial cells of rats with collagen-induced arthritis (CIA) and after intervention with disease modifying anti-rheumatic drugs (DMARDs) alone or in combination in a CIA female SD rat model induced by collagen type II. The rats were randomized to 8 groups: normal control group, CIA model control group, methotrexate (MTX, 0.9 mg/kg/w) group, cyclophosphamide (CTX, 24 mg/kg/3 w) group, leflunomide (LEF, 1.2 mg/kg/d) group, MTX + CTX group, LEF + CTX group, and MTX + LEF group. They were intervened with DMARDs alone or in combination for six weeks. The experiment lasted a total of 9 weeks in vivo. Articular inflammation was measured during the process of drug intervention in terms of the degree of swelling degree in the right hind foot using a venire caliper. All animals were sacrificed by breaking the neck after 9 weeks. Then, the ankle was fixed, decalcified, embedded, and HE stained, and prepared into slices to observe pathological changes in the synovial tissue. FAK expression in synovial cells was assayed by immunohistochemistry and the mean optical density (OD) value was measured using the HPIAS-2000 image analysis system. It was found that FAK expression was negative in normal control group, positive in CIA model control group, and decreased in the three DMARD combination treatment groups significantly as compared with that in the three single-drug groups (P < 0.05). FAK expression in LEF + CTX group or MTX + CTX group decreased more significantly than that in MTX + LEF group (P < 0.05), and there was no statistically significant difference between LEF + CTX and MTX + CTX groups. The arthritis index and pathological change in the synovial tissue in LEF + CTX group or MTX + CTX group were improved more significantly than those in MTX + LEF group or single-drug groups. Our results showed that FAK expression was positive in CIA rats, indicating that it played an important role in the pathogenesis of RA, and that intervention with DMARDs could reduce the FAK expression in synovial cells of CIA rats. We hope these findings would contribute to the treatment of RA and other rheumatic diseases by reducing adhesion, proliferation and migration of synovial cells and inhibiting the over-expression of FAK.

Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats.

Aim of the Study: This work aims to investigate the effects of HSYA on cardiac function and blood pressure., Materials and Methods: To evaluate changes in mean arterial pressure (MAP) and heart rate (HR), different groups of pentobarbitone-anesthetized normotensive and spontaneously hypertensive rats (SHR) were treated with intravenous HSYA (0.1-3 mg/kg). Isolated WKY rat hearts in Langendorff system were employed for examining the effect of HSYA on hemodynamic. After 30 min equilibration time the isolated hearts were perfused with HSYA (30 μmol/L) in a stepwise fashion. Potassium channel inhibitors were used to determine the role of potassium channel activation in HSYA effect., Results: Intravenous injection of the HSYA significantly reduced MAP and HR in both normotensive rats and SHR in a dose-dependent manner. HSYA reduced left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase of left ventricular pressure (+dp/dt(max)) and heart rate (HR) in a dose-dependent manner. HSYA had no remarkable effect on the maximum rate of decrease of left ventricular pressure (-dp/dt(max)); BK(Ca) and K(ATP) blocker can weakened the inhibitory effect of HSYA on heart function and HR, but K(V) and K(ACh) blocker did not significantly weaken the HSYA effects., Conclusion: Our results show that HSYA could significantly reduce blood pressure and heart rate, which may be related to activation of BK(Ca) and K(ATP) channels., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To explore the different effects of reinforcing and reducing methods by twirling and rotating the needle on stress-induced hypertension and its mechanism., Methods: Sixty male Wistar rats were randomly divided into a nomal group (group A), a model group (group B), an acupuncture control group (group C), an acupuncture with reinforcing method group (group D)and an acupuncture with reducing method group (group E), 12 rats in each group. The model of stress-induced hypertension was established by foot-shock and noise stimulation in the other groups except group A. Group C was treated by acupuncture at left "Taichong" (LR 3) with no manipulation, group D with twirling reinforcement method and group E with twirling reducing method at the same acupoint, respectively, and group A and B with no acupuncture treatment. The contents of calcitonin gene-related peptide (CGRP) and nitrogen monoxidum (NO) in blood plasma and hypothalamus after 7 days were observed., Results: After acupuncture treatment, the contents of CGRP in blood plasma and hypothalamus were (375.9 +/- 36.5) pg/mL and (213.6 +/- 50.1) pg/mg in group A, which were higher than (261.0 +/- 20.1) pg/mL and (156.0 +/- 21.8) pg/mg in group B , and (255.3 +/- 33.6) pg/mL and (154.3 +/- 47.3) pg/mg in group C (all P < 0.05), and (465.9 +/- 53.2) pg/mL and (250.74 +/- 47.7) pg/mg in group E higher than those in group C and (283.3 +/- 29.8) pg/mL and (164.6 +/- 47.4) pg/mg in group D (all P < 0.05), and there was no significant difference among group B, C and D (all P > 0.05). After acupuncture treatment, the contents of NO in blood plasma and hypothalamus were (43.7 +/- 5.5) micromol/L and (23.3 +/- 2.9) micromol/g in group B, (46.5 +/- 6.4) micromol/L and (23.1 +/- 3.3) micromol/g in group C, (45.8 +/- 6.7) micromol/L and (25.0 +/- 2.7) micromol/g in group D, which were all lower than (64.5 +/- 9.9) micromol/L and (30.7 +/- 1.6) micromol/g in group A (all P < 0.05), (55.9 +/- 4.6) micromol/L and (30.4 +/- 2.1) micromol/g in group E higher than those in group C and group D (all P < 0.05), and there was no significant difference among group B, C and D either (all P > 0.05)., Conclusion: Acupuncture with twirling reducing method can increase the contents of CGRP and NO in rats with stress-induced hypertension, thereby causing a fall in blood pressure, however, no significant influence with twirling reinforcing method. Reinforcing or reducing method by twirling and rotating the needle has different efficacy.

To clarify whether apoptosis is involved in the injury processes induced by autoantibody against cardiac beta1-adrenoceptor, we investigated the biological and apoptotic effects of antibodies on cultured neonatal rat cardiomyocytes. Wistar rats were immunized with peptides corresponding to the second extracellular loop of the beta1-adrenoceptor to induce the production of anti-beta1-adrenoceptor antibodies in the sera. Immunoglobulin (Ig) G in the sera was detected using synthetic antigen enzyme-linked immunosorbent assay and purified using the diethylaminoethyl cellulose ion exchange technique. Apoptosis of cardiomyocytes was evaluated using agarose gel electrophoresis and flow cytometry. Our results showed that the positive serum IgG greatly increased the beating rates of cardiomyocytes and showed an agonist-like activity. Furthermore, positive serum IgG induced cardiomyocyte apoptosis after treatment with beta1-adrenoceptor overstimulation for 48 h. The effects of monoclonal antibody against beta1-adrenoceptor were also found to be similar to those of positive serum IgG. It was suggested that the autoantibody could induce cardiomyocyte apoptosis by excessive stimulation of beta1-adrenoceptor.

Using two-kidney one-clip renal hypertensive (2K1C group), stress-induced hypertensive (neural group), DOCA-salt treated hypertensive (DOCA group) and spontaneously hypertensive rats (SHR group), to investigate the change in AT(1A)-receptor autoantibodies (AT(1A)-AAs) during the development of the four types of hypertension. The biological activities of AT(1A)-AAs were examined. It was shown that the frequency of occurrence and titres of AT(1A)-AAs increased significantly during the development of hypertension. In the four hypertensive groups studied, the occurrence of AT(1A)-AAs was most prominent in SHR, 2K1C and neural groups. The biological effects of AT(1A)-AAs were shown to increase the beating frequency of cultured neonatal myocardial and vascular contractile tension. It is suggested that autoimmune mechanisms are involved the pathogenesis of different types of hypertension and the AT(1A)-AAs may be one of the mechanisms leading to cardiac hypertrophy.

The purpose of this study was to compare the vasodilating effects of angiotensin-(1-7) [Ang-(1-7)] on the different vessels and to clarify its mechanisms by using relaxing responses of preconstricted vascular rings. The results showed: (1) Ang-(1-7) dose-dependently induced vasorelaxation in all the vessels studied. However, there is apparent heterogeneity in the responsiveness of vessels from different origin. (2) The Ang-(1-7)-induced vasorelaxation was endothelium dependent and largely mediated by NO system. (3) The vasodilator action of Ang-(1-7) was not mediated by AT1 or AT2 receptor subtypes. It is suggested that the Ang-(1-7)-induced vasorelaxation is endothelium dependent by some other unclarified angiotensin receptor subtypes and is largely mediated by NO system.

In an experimental rat's renovascular hypertension model, we studied the genesis of anti-cardiac beta1-adrenoceptor and M2-muscarinic receptor autoantibodies in relation to the changes in immunological function during the development of renal hypertension. The biological activities of these autoantibodies were also examined. It was shown that after two weeks of operation both the frequency of occurrence and the titre of autoantibodies to cardiac beta1-adrenoceptor and M2-muscarinic receptor were significantly increased as compared with the control of pre-treatment. The increased autoantibodies lasted for several weeks and then automatically decreased gradually to the pre-clipping level at 10 weeks. Meanwhile the ratio of CD4+/CD8+ was also undergone an initial increase followed by gradual recovery and correlated well with the changes in antibody titre. The biological effects of these autoantibodies displayed an "gonistic-like" activities on the beating frequency of cultured neonatal cardiomyocyte. It is suggested that autoimmune mechanisms are involved in the pathogenesis of renal hypertension and the cardiac receptor autoantibodies might be one of the mechanisms leading to cardiac dysfunction.

Aim and Methods: The effects of losartan (after operation 2 week to 10 week, 5 mg/kg d ig) on generation of AT1R-AA in sera were observed during development of hypertension in rats. The renovascular hypertension (RVH) model was established by two-kidney one-clip method, a synthetic peptide corresponding to amino acid sequence 165-191 of the second extracellular loop of the angiotensin II-1 receptor (AT1R) was used as antigen, SA-ELISA were used to examine sera AT1R autoantibody (AT1R-AA)., Results: The frequencies and titres of AT1R-AA after operation one week rats were significantly increased (P < 0.05). The treatment with losartan not only inhibited structural and functional changes, but also the frequencies and titres of AT1R-AA was significantly lower (P < 0.05) than RVH group., Conclusion: It is suggested that the losartan significantly inhibits generation of the AT1R-AA.

Previous studies have shown that ischemia and reperfusion are potent stimuli for eliciting cardiomyocyte apoptosis, and that polymorphonuclear leukocytes (PMNs) are involved in the development of myocardial injury induced by ischemia and reperfusion. The present study examined whether PMN could directly induce cardiomyocyte apoptosis and, if so, it possible signal transduction pathways. In addition, we also investigated the effects of carvedilol, a potent antioxidant, on PMN-induced apoptosis. Cultured primary neonatal rat cardiomyocytes were exposed to PAF-activated PMNs at concentrations of 10(5), 3 x 10(5) and 10(6) cells/well for 48 h. Multiple detecting techniques, including electron microscopy, DNA gel electrophoresis. TUNEL assay and flow cytometry were used to identify myocyte apoptosis. All of these techniques demonstrated that activated PMNs directly induced cardiomyocyte apoptosis in a concentration-dependent manner, while unactivated PMNs showed no such effect. Activated PMN-induced apoptosis was partially inhibited by SB203580, a specific inhibitor of the p38-MAPK signaling system. Carvedilol (at a dose range of 1-10 mumol/l) significantly prevented activated PMN-induced cardiomyocyte apoptosis. These results suggest that PMNs, when activated, directly induce cardiomyocyte apoptosis and that the p38-MAPK signaling pathway might be involved in this process. Carvedilol may prevent PMN-induced apoptosis possibly because of its antioxidant properties.

The aim of this study was to observe the change in angiotensin II receptor subtype 1 (AT(1)) autoantibody during the development of renovascular hypertension (RVH). The Goldblatt renovascular hypertension model was established by the two-kidney one-clip method, and a synthetic peptide corresponding to amino acid sequence 165-191 of the second extracellular loop of the AT(1)-receptor was used as the antigen. Sera AT(1)-receptor autoantibody was detected by SA-ELISA. It was shown that two weeks after operation both the frequency of occurrence and the titre of autoantibodies to AT(1)-receptor were significantly increased as compared with the pre-treatment control. The increase in autoantibodies lasted several weeks and then decreased gradually to the pre-clipping level at 12 weeks. It is suggested that autoimmune mechanisms are involved in the pathogenesis of renovascular hypertension and the AT(1) autoantibodies may be one of the mechanisms leading to cardiac hypertrophy.

The effects of insulin-like growth factor I (IGF-I) on cardiomyocyte apoptosis induced by hypoxia in cultured neonatal rat cardiomyocyte were investigated. Primary neonatal rat cardiomyocytes were cultured in 95% N2-5% CO2 to imitate the in vivo hypoxic condition. Electron microscopic observation revealed a series of typical morphological changes characteristic of apoptosis in cardiomyocytes under the hypoxic condition. DNA gel electrophoresis showed DNA laddering in an ischemic duration-dependent manner. The hypoxia-induced cardiomyocyte apoptosis was also evidenced by flow cytometry and TUNEL assay. DNA gel electrophoresis showed that IGF-I in a dose range of 10(-9)-10(-7) mol/l could significantly prevent the hypoxia-induced cardiomyocyte apoptosis. The protective effects of IGF-I against hypoxia-induced apoptosis could also be verified by flow cytometry and TUNEL assay. A tyrosine kinase inhibitor (genistein), a MAPK inhibitor (PD-098059) and a P13 kinase inhibitor (wortmannin) could also suppress the antiapoptotic effects of IGF-I. These results suggest that IGF-I can directly alleviate the hypoxia-induced cardiomyocyte apoptosis and that the three kinase routes mentioned above may be involved in its signaling pathways.

Objective: To study the effect of tetrahydroberberine (THB) on the peripheral vascular dopamine DA1 and DA2 receptors., Method: Using isolated vascular rings method., Result: THB(0.1-10 mumol.L-1) shifted the dose-response curves to the right in a nonparallel fashion and decreased the maximal response (Emax) of both the fenoldopam(FODA, a selective DA1 agonist)-induced and the propyl-butyl-dopamine(PBDA, a selective DA2 agonist)-induced vasorelaxation, showing a non-competitive antagonistic action. The pD'2 values of THB for FODA in the renal, pulmonary and mesenteric arteries were 5.29, 5.37 and 5.46, respectively, while for PBDA in the mesenteric and femoral arteries were 5.53 and 5.48, respectively. The potencies of this antagonistic action were weaker than those of SCH23390, a selective DA1 antagonist, domperidone, a selective DA2 antagonist and l-SPD, a mixed DA1/DA2 antagonist, domperidone, a selective DA2 antagonist and l-SPD, a mixed DA1/DA2 antagonist., Conclusion: THB is a mixed peripheral DA, and DA2 receptor antagonist similar to l-SPD.

Autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic receptors have mainly been found in the sera of patients with idiopathic dilated cardiomyopathy (DCM). In order to elucidate the pathological significance of these autoantibodies in DCM, it is necessary to understand their characteristic distribution in a healthy population of different genders and ages. The peptides corresponding to the sequences of the second extracellular loops of the human beta1-adrenoceptor and M2-muscarinic receptors were therefore used as antigens to screen the sera of 408 healthy subjects of different ages (ranging from 0.5 to 85 years). Of 408 sera, 41 (10.0%) and 46 (11.3%) recognized the beta1-adrenoceptor and M2-muscarinic receptor peptides respectively. Of the positive sera for beta1-adrenoceptors and M2-muscarinic receptors, up to 63.4% and 56.5% had both anti-beta1-adrenoceptor and anti-M2-muscarinic receptor autoantibodies respectively. The antibody titres of the positive sera of healthy subjects were all of a low level, with a geometric mean titre of 1:42+/-1.9 for anti-beta1-adrenoceptor antibodies and 1:51+/-1.7 for anti-M2-muscarinic receptor antibodies. The frequency of occurrence of autoantibodies to both receptors in the sera of healthy subjects increased significantly with age. In conclusion, the autoantibodies to beta1-adrenoceptors and M2-muscarinic receptors in the sera of healthy subjects are characterized by a low frequency of occurrence and low titre, with the frequency of occurrence increasing with age.