The value of radiomics based on dual-energy CT for differentiating benign from malignant solitary pulmonary nodules.

OBJECTIVE: To investigate the value of monochromatic dual-energy CT (DECT) images based on radiomics in differentiating benign from malignant solitary pulmonary nodules. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and informed consent was waived. Pathologically confirmed lung nodules smaller than 3 cm with integrated arterial phase and venous phase (AP and VP) gemstone spectral imaging were retrospectively identified. After extracting the radiomic features of each case, principal component analysis (PCA) was used for feature selection, and after training with the logistic regression method, three classification models (ModelAP, ModelVP and ModelCombination) were constructed. The performance was assessed by the area under the receiver operating curve (AUC), and the efficacy of the models was validated using an independent cohort. RESULTS: A total of 153 patients were included and divided into a training cohort (n = 107) and a validation cohort (n = 46). A total of 1130 radiomic features were extracted from each case. The PCA method selected 22, 25 and 35 principal components to construct the three models. The diagnostic accuracy of ModelAP, ModelVP and ModelCombination was 0.8043, 0.6739, and 0.7826 in the validation set, with AUCs of 0.8148 (95% CI 0.682-0.948), 0.7485 (95% CI 0.602-0.895), and 0.8772 (95% CI 0.780-0.974), respectively. The DeLong test showed that there were significant differences in the AUCs between ModelAP and ModelCombination (P = 0.0396) and between ModelVP and ModelCombination (P = 0.0465). However, the difference in AUCs between ModelAP and ModelVP was not significant (P = 0.5061). These results demonstrate that ModelCombination shows a better performance than the other models. Decision curve analysis proved the clinical utility of this model. CONCLUSIONS: We developed a radiomics model based on monochromatic DECT images to identify solitary pulmonary nodules. This model could serve as an effective tool for discriminating benign from malignant pulmonary nodules in patients. The combination of arterial phase and venous phase imaging could significantly improve the model performance.

Multispecies comparative analysis reveals transcriptional specificity during Mongolian horse testicular development.

Mongolian horses have been bred and used for labor and transport for centuries. Nevertheless, traits of testicular development in Mongolian horses have rarely been studied; particularly, studies regarding the transcriptional regulation characteristics of testicular development are lacking. In this paper, transcription specificity during testicular development in Mongolian horses is highlighted via a multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA). Interestingly, the results showed that most genes were up-regulated in the testes after sexual maturity, which is a phenomenon conserved across species. Moreover, we observed nine key genes involved in regulating Mongolian horse testicular development. Notably, unique transcription signatures of testicular development in Mongolian horses are emphasized, which provides a novel insight into the mechanistic study of their testicular development.

Strategy for Achieving Long-Wavelength Near-Infrared Luminescence of Diimineplatinum(II) Complexes.

Although many strategies have been used to help design effective near-infrared (NIR) luminescent materials, it is still a huge challenge to realize long-wavelength NIR luminescence of diimineplatinum(II) complexes in the solid state. Herein, we have successfully achieved long-wavelength NIR luminescence of a family of diimineplatinum(II) complexes based on a new strategy that combines a one-dimensional (1D) "Pt wire" structure with the electronic effect of the substituent. The structures of six solvated diimineplatinum(II) complexes based on 4,4-dichloro-2,2'-bipyridine or 4,4-dibromo-2,2'-bipyridine and 4-substituted phenylacetylene ligands have been determined, namely, 1·1/2toluene, 2·1/2THF, 3·1/8toluene, 4·1/2THF, 5·1/8CH2Cl2, and 6·1/4toluene. All of them crystallize in the monoclinic space group C2/c or C2/m and stack in the 1D "Pt wire" structure. In the solid state, six complexes exhibited unusual long-wavelength metal-metal-to-ligand charge-transfer luminescence that peaked at 984, 1044, 972, 990, 1022, and 935 nm, respectively. Interestingly, 2·1/2THF has the shortest Pt···Pt distance and the longest emission wavelength among the six complexes. As far as we know, the luminescence of 2·1/2THF at 1044 nm is the longest emission wavelength among known diimineplatinum(II) complexes. Systematic studies revealed that good molecular planarity, suitable substituent position, weak hydrogen-bond-forming ability of the substituents, appropriate molecular bending, and weakening of the interaction between solvated molecules and platinum molecules are conducive to the construction of a 1D "Pt wire" structure of the diimineplatinum(II) complex. Furthermore, the emission energy of the complex is mainly determined by the strength of the Pt-Pt interaction and electronic effect of the substituent.

A Trichromatic and White-Light-Emitting MOF Composite for Multi-Dimensional and Multi-Response Ratiometric Luminescent Sensing.

Present here is a new dual ratiometric luminescent probe D which is a trichromatic and white-light-emitting metal-organic framework (MOF) composite facilely obtained by incorporating red/green-emitting complex modules into a blue-emitting MOF. Probe D exhibits remarkable capabilities of sensing different volatile organic solvents (VOSs) via 2D code recognition of the two VOS-dependent MOF ligand-to-module ratios of the emission-peak intensities. For specific VOSs, the resultant luminescent color changes from the starting white color are sharp enough to be visible to the naked eye. Remarkably, D can differentiate solution-phase nitroaromatics and metal ions by recording the evolution of the two ratios during titration processes, enabling an unusual 3D code recognition using the titrant amount as the third dimension for the first time. D also can be used to detect dinoseb, Fe3+ and Al3+ ions quantitatively by analysis of the ratios with detection limits as low as 0.050, 0.41, and 0.12 ppm, respectively. Clearly, such a self-referencing trichromatic probe can maximize the output information and significantly enhance the detection selectivity and sensitivity via multi-dimensional sensing, and has great potentials for practical applications.

Ischemic postconditioning decreases matrix metalloproteinase-2 expression during ischemia-reperfusion of myocardium in a rabbit model: A preliminary report.

OBJECTIVE: To investigate the effect of ischemic postconditioning on the expression of matrix metalloproteinase (MMP)-2 during ischemia-reperfusion of myocardium in a rabbit model. METHODS: Thirty-six male New Zealand white rabbits were randomly divided into sham, ischemia-reperfusion and ischemic postconditioning groups. Myocardial ischemia-reperfusion was created by ligating the left anterior descending coronary artery for 30 min followed by 3 h of reperfusion. Myocardial infarction sizes were determined by dual staining with triphenyltetrazolium chloride and trypan blue. Plasma levels of MMP-2 were measured using ELISA. Myocardial MMP-2 messenger RNA was analyzed by reverse transcription polymerase chain reaction. RESULTS: The mean (± SD) infarct size in the ischemic postconditioning group was significantly smaller compared with the ischemia-reperfusion group (37.1±3.8% versus 57.5±1.9%; P=0.02). The incidence of ventricular tachycardia in the ischemic postconditioning group was also lower than in the ischemia-reperfusion group (8.5% versus 75%; P=0.003). MMP-2 messenger RNA expression in the ischemic postconditioning group was significantly lower compared with the ischemia-reperfusion group (0.4944±0.0476 versus 0.6989±0.0694; P=0.02). CONCLUSION: Ischemic postconditioning reduces myocardial ischemia-reperfusion injury, possibly by inhibiting the expression of MMP-2.

Recombinant B-type natriuretic peptide nesiritide attenuates vascular remodelling by reducing plasma aldosterone in rabbits.

BACKGROUND: This study was designed to investigate the effect of nesiritide, a recombinant B-type natriuretic peptide (BNP), on plasma aldosterone and vascular remodelling following balloon-induced endothelial injuries to the iliac arteries. METHODS: Twenty-four male New Zealand rabbits were divided into nesiritide (0.1mg/kg/day, sc, for 4 weeks, n=12) and saline-treated control group (n=12). A balloon catheter was inserted to the right iliac artery to induce endothelia injuries. Plasma aldosterone was measured before and 28 days after the treatment by radioimmunoassay. RESULTS: The area under internal elastic membrane (657.1±129.6 vs 486.7±124.0µm(2), P=0.02) and the area under external elastic membrane (1506.2±188.3.9 vs 1185.0±202.9µm(2), P=0.02) in the nesiritide group were greater than in the control group. The stenosis ratio in the nesiritide group was lower than in the control group (20.1±6.2% vs 39.6±9.5%, P=0.01). The plasma levels of aldosterone (2.03±0.31 vs 3.00±0.29ng/L, P<0.01) in the nesiritide group was lower than in the control group. Pearson's correlation analysis showed a positive correlation between the levels of plasma aldosterone and the stenosis ratio of the injured right iliac arteries (r=0.622, P=0.002). CONCLUSION: Nesiritide treatment reduced stenosis ratio of the rabbit iliac artery following balloon-induced endothelial injuries, and the reduced stenosis ratio was associated with a reduction in the plasma aldosterone concentrations.

[Comparison of mannitol and hypertonic saline in treatment of intracranial hypertension of rabbits].

OBJECTIVE: To compare the effects of mannitol and hypertonic saline (HS) in treatment of intracranial hypertension (ICH) of rabbits. METHODS: The animal mode of ICH was established by perfusing artificial cerebrospinal fluids (aCSF) with controlled pressure into the cerebral ventricles of rabbits. The mean arterial pressure, respiratory rate, tidal volume, perfusion rate of aCSF and water content of cerebrum were investigated in rabbits with ICH after a single bolus of 20% mannitol (5 ml/kg), 7.5% HS (2.2 ml/kg) or 23.4% HS (2.2 ml/kg). RESULTS: After the intracranial pressure was elevated from 15 cmH2O to 75 cmH2O, the mean arterial pressure was increased and the tidal volume was decreased. After treatment by 20% mannitol, 7.5% HS or 23.4% HS, the increased percentage of mean arterial pressure and the decreased percentage of tidal volume were similar to the changes in control group. However, the perfusion rate of CSF was increased and water content of cerebrum was decreased after treatment by either 20% mannitol or 23.4% HS, but not by 7.5% HS. No different effects were found between 20% mannitol and 23.4% HS. CONCLUSION: With the similar osmotic burden, 20% mannitol is more effective in treating ICH than 7.5% HS. With higher osmotic load, the efficacy of HS is enhanced, and 23.4% HS may be used as an alternative to mannitol in treatment of ICH.

[Responses of spatial distribution pattern of the dominant population Artemisia ordosica to enclosure restoration in desert steppe.] / è’æ¼ è‰åŽŸä¼˜åŠ¿ç§ç¾¤æ²¹è’¿ç©ºé—´åˆ†å¸ƒæ ¼å±€å¯¹å°è‚²æ¢å¤çš„å“åº”.

Shrubs play an important role in maintaining biodiversity, stability and ecological service in grassland. Exploring the effects of enclosure on dominant shrub population can provide scientific guidance for grassland restoration and tending management. In this study, we investigated main growth characteristics and spatial distribution pattern of Artemisia ordosica population in four enclosed grasslands with duration of 0, 5, 15, and 25 years. The results showed that population density increased first and then decreased with time extension, and peaked after enclosed for 15 years, which was 3.7 times that of unenclosed plot. The crown and projected area showed opposite responses trend to that of density, which decreased by 31.7% and 52.3% after enclosed 15 years, respectively. The height decreased by 25.3% after 5 years of enclosure, and then increased gradually. Semi-variance function analysis showed that population distribution in all grasslands conformed to Gaussian model. The spatial variation decreased gradually in the early stage of enclosure, and then increased after enclosed for 15 years. Structure ratio in each plot was higher than 0.75, but nugget was relatively small, indicating that spatial autocorrelation of population was mainly affected by structural factors rather than random factors. Spatial distribution of A. ordosica population was patchy and striped. Enclosure reduced spatial variation of population at small scale. However, spatial heterogeneity and scale dependence of population enhanced after enclosed 25 years as plaque dissociating. Our findings suggest that enclosure duration is the key factor affecting plant growth and spatial distribution of dominant population in desert steppe. Long-term fencing enhances the spatial heterogeneity of dominant population. Appropriate human intervention should be carried out after 15 years of enclosure.

Bioequivalence evaluation and food effect assessment of Lisinopril/amlodipine tablets in healthy Chinese subjects under fasting and fed conditions.

PURPOSE: The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects. METHODS: A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (Cmax) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded. RESULTS: Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80-1.25. A high-fat meal appeared to decrease the Cmax and AUC of lisinopril. No severe adverse events were observed. CONCLUSION: The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions. TRIAL REGISTRATION: Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).

Pharmacokinetics and Bioequivalence of Sitagliptin Phosphate/Metformin Hydrochloride Tablets in Healthy Chinese Subjects: A Randomized, Open-Label, Crossover Study.

OBJECTIVE: Our objective was to evaluate the pharmacokinetics and bioequivalence of test and reference (JANUMET®) formulations of sitagliptin phosphate/metformin hydrochloride tablets at a single dose of 50 mg/850 mg. METHODS: The study was a randomized, open-label, two-period, double-crossover trial. Volunteers under fasting (n = 24) and fed (n = 24) conditions were given a single oral dose of test or reference formulations of sitagliptin phosphate/metformin hydrochloride tablets 50 mg/850 mg. We used the liquid chromatography tandem mass spectrometry method to determine the concentrations of sitagliptin and metformin in the plasma of subjects. Pharmacokinetic metrics were calculated using the WinNonlin 7.0 program, and bioequivalence was evaluated using SAS 9.4. RESULTS: Under the fasting condition, the 90% confidence intervals (CIs) of geometric mean ratio for maximum plasma drug concentration (Cmax), area under the plasma concentration-time curve from time zero to time t (AUC0-t), and AUC from time zero to infinity (AUC0-∞) of sitagliptin between the test and reference groups were 101.70-120.62%, 99.81-105.61%, and 100.27-106.12%, respectively; for metformin, they were 90.39-111.48%, 94.76-109.12%, and 95.76-110.38%, respectively. Under the fed condition, they were 102.12-117.31%, 100.80-107.81%, and 100.82-107.78%, respectively, for sitagliptin and 95.53-105.22%, 92.76-103.07%, and 93.40-104.14%, respectively, for metformin. Both were generally well-tolerated. CONCLUSION: The two formulations of sitagliptin phosphate/metformin hydrochloride tablets were bioequivalent under fasting and fed conditions in healthy Chinese subjects.

Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers.

BACKGROUND AND INTRODUCTION: SHR6390 is a new developed highly effective and selective small-molecule oral CDK4/6 inhibitor. We aimed to evaluate the effect of food on the pharmacokinetics of SHR6390 tablets. METHODS: In an open-label two-way crossover study, 24 healthy Chinese volunteers were randomly divided into Group A and Group B, and 12 volunteers in each group received a single oral dose of a SHR6390 150-mg tablet under fasting and high-fat conditions. Blood samples were collected and determined for pharmacokinetic analyses. A liquid chromatography-tandem mass spectrometry method was developed and validated for determining the SHR6390 concentration. RESULTS: The time to maximum plasma concentration was not significantly affected by a high-fat diet. Compared with the fasting group, maximum plasma concentration, i.e., the area under the concentration-time curve (AUC0-t and AUC0-∞) was altered significantly, as evidenced by an increase of 56.9%, 38.6%, and 37.5% respectively. We identified seven metabolites of SHR6390 from the plasma samples, and we found no sex differences in metabolic pathways. All treatment-emergent adverse events were Grade 1 or 2. CONCLUSIONS: Food intake increased the maximum plasma concentration, AUC0-t, and AUC0-∞ significantly compared with the fasting condition. Meanwhile, single-dose SHR6390 for two treatment cycles is safe. SHR6390 was administered in a fasting status in the pivotal phase III study (NCT03927456) and chosen for the final drug label.

Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis.

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.

[The expression and significance of signal regulatory protein a1 in autoimmune hepatitis].

OBJECTIVE: To observe the expression change of signal regulatory protein alpha1 (SIRPalpha1) in autoimmune hepatitis (AIH) and approach the relationship between SIRPalpha1 and the extent of inflammation. METHODS: Immunohistochemistry is used to detect the expression of SIRPalpha1 in the paraffin section preparations of 33 AIH and 10 normal hepatic tissue. RESULTS: SIRPalpha1 is positive or weakly positive expressed in AIH. The staining is localized in the cytoplasm of Kupffer cells in the hepatic sinusoid with focal distribution. It is negative in normal hepatic tissue. In light AIH, it is negative or weakly positive expressed with a 36.4 percent of the positive rate (4/11). The positive or strong positive expression is found in the moderate AIH with an 84.2 percent of the positive rate(16/19). There is statistical significance between both light AIH, moderate AIH and severe AIH (P less than 0.001) and moderate AIH and light AIH (P less than 0.001). There is no statistical significance between both light AIH and severe AIH (P = 0.145 ) and moderate AIH and severe AIH (P = 0.084). CONCLUSIONS: As a negative regulatory factor, the expression of SIRPalpha1 in hepatic sinusoid Kupffer cells is some associated with the extent of AIH.

Nucleated red blood cells participate in myocardial regeneration in the toad Bufo Gargarizan Gargarizan.

Heart regeneration is negligible in humans and mammals but remarkable in some ectotherms. Humans and mammals lack nucleated red blood cells (NRBCs), while ectotherms have sufficient NRBCs. This study used Bufo gargarizan gargarizan, a Chinese toad subspecies, as a model animal to verify our hypothesis that NRBCs participate in myocardial regeneration. NRBC infiltration into myocardium was seen in the healthy toad hearts. Heart needle-injury was used as an enlarged model of physiological cardiomyocyte loss. It recovered quickly and scarlessly. NRBC infiltration increased during the recovery. Transwell assay was done to in vitro explore effects of myocardial injury on NRBCs. In the transwell system, NRBCs could infiltrate into cardiac pieces and could transdifferentiate toward cardiomyocytes. Heart apex cautery caused approximately 5% of the ventricle to be injured to varying degrees. In the mildly to moderately injured regions, NRBC infiltration increased and myocardial regeneration started soon after the inflammatory response; the severely damaged region underwent inflammation, scarring, and vascularity before NRBC infiltration and myocardial regeneration, and recovered scarlessly in four months. NRBCs were seen in the newly formed myocardium. Enzyme-linked immunosorbent assay and Western blotting showed that the levels of tumor necrosis factor-α, interleukin- 1ß, 6, and11, cardiotrophin-1, vascular endothelial growth factor, erythropoietin, matrix metalloproteinase- 2 and 9 in the serum and/or cardiac tissues fluctuated in different patterns during the cardiac injury-regeneration. Cardiotrophin-1 could induce toad NRBC transdifferentiation toward cardiomyocytes in vitro. Taken together, the results suggest that the NRBC is a cell source for cardiomyocyte renewal/regeneration in the toad; cardiomyocyte loss triggers a series of biological processes, facilitating NRBC infiltration and transition to cardiomyocytes. This finding may guide a new direction for improving human myocardial regeneration.

Treatment with nesiritide, a recombinant B-type natriuretic Peptide, reduces vascular remodeling following balloon-induced endothelial injuries in rabbits.

Re-stenosis or remodeling of coronary and peripheral arteries remains a major complication following balloon-angioplasty or stenting. This study was designed to investigate the effect of nesiritide, a recombinant B-type natriuretic peptide (BNP), on vascular remodeling following balloon-induced endothelial injuries. Twenty-eight male New Zealand rabbits were divided into nesiritide-treated (0.1 mg/kg/day, sc, for 4 weeks, n = 10), saline-treated control (n = 10) and sham-operated groups (n = 8). In the nesiritide and control groups, a balloon catheter was inserted to the right iliac artery to induce injuries. Vascular endothelial growth factor (VEGF) was measured by immunohistochemistry. The area under internal elastic membrane of the arterial wall (643.2 ± 134.1 vs 493.7 ± 139.3 µm(2), p < 0.05) and the area under external elastic membrane (1495.1 ± 204.9 vs 1265.9 ± 232.6 µm(2), p < 0.05) in the nesiritide group were greater than those in the control group, but were smaller than those in the sham-operated group (p < 0.05). The stenosis ratio was lower in the nesiritide group than in the control group (18.7 ± 7.7% vs 38.0 ± 8.3%, p < 0.01). Importantly, the VEGF expression rate was significantly lower in the nesiritide group than in the control group (42.2 ± 8.8% vs 56.1 ± 13.1%, p < 0.05), while there were no signs of VEGF expression in the non-injured arteries of the three groups. In conclusion, nesiritide treatment reduces the stenosis of the rabbit iliac artery following balloon-induced endothelial injuries probably by decreasing VEGF expression.

Discrimination of Various Amine Vapors by a Triemissive Metal-Organic Framework Composite via the Combination of a Three-Dimensional Ratiometric Approach and a Confinement-Induced Enhancement Effect.

Multiemissive sensors are being actively pursued, because of their ratiometric luminescent detection capabilities, which demonstrates better sensitivity and selectivity than conventional single-emission sensors. Herein, we present a trichromatic white-light-emitting metal-organic framework (MOF) composite (Z3) by simultaneously incorporating red/green-emitting Pt/Ru complex cations into porous blue-emitting bio-MOF-1 through post-synthetic modification. With the help of a three-dimensional (3-D) dual-ratiometric luminescence recognition method, and unique turn-on responses of the red emission toward amine compounds (ACs), including NH3 and aliphatic amines, via confinement-induced luminescence enhancement effect, Z3 can work as a dual-ratiometric luminescent sensor for discrimination of 7 out of 11 AC vapors. This work not only provides a new AC sensing mechanism (confinement effect) that can induce a "turn-on" response but also proves that the accuracy and selectivity of composite sensor can be greatly improved through the combination of 3-D recognition method and the confinement effect. Thus, it open up fresh opportunities to develop composite sensors with excellent sensing and differentiating ability.

Icariin treatment reduces blood glucose levels in type 2 diabetic rats and protects pancreatic function.

Icariin, a flavonoid isolated from traditional oriental herbal medicines, has been demonstrated to exhibit several health benefits in animal models and in humans. The aim of the present study was to investigate the effect of Icariin on hyperglycemia in type 2 diabetes mellitus (T2DM) in rats. A model of diabetes was established in 50 Sprague Dawley rats using a high-sugar and high-fat diet and peritoneal injection of streptozotocin. Diabetic rats were divided into five groups: Diabetic control; metformin; and rats treated with three different doses of Icariin, 5, 10 and 20 mg/kg. Body weight and blood glucose levels were measured, and serum adiponectin levels, expression of phospho-AMP mediated protein kinase (p-AMPK) and glucose transporter isoform 4 (GLUT-4) were measured using ELISA, Realtime PCR and western blotting, respectively. Diabetic rats without drug treatment exhibited reduced body weight, increased blood glucose levels and decreased the number of islets. In T2DM rats treated with 10 or 20 mg/kg Icariin, the blood glucose levels were reduced, whereas serum adiponectin levels were not affected. Additionally, the mRNA and protein expression levels of p-AMPK and GLUT-4 protein were increased in the T2DM rats treated with Icariin. In conclusion, in the diabetes rat model, Icariin alleviated the severity of diabetes, and the effects may be associated with reduction of hyperglycemia by activating an AMPK/GLUT-4 pathway.

Interleukin-2 enhances the cytotoxic activity of circulating natural killer cells in patients with chronic heart failure.

Our objective was to investigate the effect of interleukin-2 (IL-2) on the cytotoxic activity of natural killer (NK) cells in patients with chronic heart failure (CHF). Natural killer cells were isolated from 48 patients with CHF and 30 healthy subjects. The cytotoxic activities of the NK cells were assessed with the thiazolyl blue tetrazolium bromide (MTT) approach. Interleukin-2 (20 ng/ml) was added to the cell culture to stimulate the cytotoxicity of the NK cells. The cell number in the New York Heart Association (NYHA) class II, III, and IV was 27.9 +/- 2.5, 21.2 +/- 2.7, and 16.8 +/- 2.6 cells/microl, respectively, which was significantly lower than in the control group (31.2 +/- 3.6 cells/microl, all P < 0.01). The cytotoxic activities in NYHA II, III, and IV groups were 28.6% +/- 3.2%, 16.0% +/- 2.2%, and 12.1% +/- 2.9%, respectively, which was lower than in the control group (41.0% +/- 4.0%, all P < 0.01). Univariate analysis showed a close correlation between the NK cell cytotoxicity and the left ventricular ejection fraction (r = 0.949, P < 0.001). After in vitro treatment with IL-2, there was a significant increase in the cytotoxic activity of the NK cells in the control and the three heart failure groups (all P < 0.01). There is a significant reduction in the number and the cytotoxic activity of circulating NK cells in patients with CHF. The degree of NK cell deficiency is closely related to the severity of left ventricular dysfunction. In vitro treatment with IL-2 improves the cytotoxic activity of NK cell from the CHF patients.

Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters.

AIM: To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma (ICC). METHODS: An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS: The expression of E-cadherin and P120 was reduced in 27 cases (64.3%) and 31 cases (73.8%), respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade (chi2 = 9.333, P = 009 and chi2 = 11.71, P = 0.003), TNM stage (chi2= 8.627, P = 0.035 and chi2 = 13.123, P = 0.004), intrahepatic metastasis (chi2= 7.292, P = 0.007 and chi2 = 4.657, P = 0.041, respectively) and patients' survival (chi2= 6.351, P = 0.002 and chi2 = 4.023, P = 0.000, respectively). In addition, the expression of P120 was in concordance with that of E-cadherin (chi2 = 13.797, P = 0.000), indicating that the expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model (r = 0.088, P = 0.049). CONCLUSION: Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients' survival, but only P120 is an independent prognostic factor for ICC.

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas.

AIM: To examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/catenin complex and clinicopathologic parameters of HCC patients. METHODS: An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS: Reduced expression of E-cadherin, alpha-, beta-, gamma-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively). A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively). In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P = 0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with alpha-, beta-, gamma-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION: Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.