This article has illuminated the importance of strengthening discipline construction to the the local colleges and universities,and why Guangdong Pharmaceutical University should take all kinds of measures to serve the development of territorial economy and improve the characteristic for operating the universities.

Objective To determine the effects of Hyperoside ( Hyp) on the memory impairment induced by hypobaric hypoxia. Meth-ods SD rats were exposed in hypobaric hypoxia chamber which simulated 6 100 m high altitude for 7 days to induce memory impairment. Morris maze was applied to determine the effects of Hyp on memory in hypobaric chamber. The activities of SOD and CAT and levels of GSH and MDA in rat hippocampus were measured by assay kit ( Nanjing Jiancheng Bioengineering Institute) . Results In target quadrant,the time and path and the frequency to cross platform were reduced under hypobaric hypoxia as compared with normoxia group ( P < 0. 05 or P<0. 01). Administration of Hyp significantly attenuated the hypoxia-induced the memory impairment responses(P<0. 05 or P<0. 01). The activities of SOD and CAT in rats hippocampus exposed to hypobaric hypoxia were significantly improved in the presence of Hyp as com-pared with the absence of Hyp(P<0. 05 or P<0. 01),so did GSH level (P<0. 05 or P<0. 01). Significant decrease of MDA levels was observed in the hippocampus on exposure to hypobaric hypoxia with Hyp as compared without Hyp. Conclusion Hyp reduces hypoxia-in-duced oxidative stress injury by upregulating activity of antioxidant proteins such as SOD,CAT in hippocampus of rats, which contribute to at-tenuate memory impairment induced by hypobaric hypoxia.

Objective To evaluate the effect and mechanism of bone morrow MSCs transplantation in swine with AMI by cell biology and molecular imaging methods including PET/CT, SPECT, and MRI. Methods Twenty?four Chinese mini?swine ( ( 25 ± 5 ) kg ) were randomly divided into 2 groups: MSCs group ( n=12) and control group ( n=12) . Myocardial infarction was induced in swine hearts by occlusion of the LAD. Thirty minutes later, the MSCs group received autologous MSCs transplantation through in?tramyocardial injection into the peri?infarcted areas (2×107,2 ml) and the control group was subjected to cell culture medium in the same way. At the 1st and 4th weeks after MSCs transplantation, myocardial glu?cose metabolism, myocardial perfusion and cardiac function were evaluated in the two groups through PET/CT, SPECT and MRI. The minimum FDG mean signal intensity ( MSI ) , summed MSI, SRS, SRS%, LVEF, ESV, stroke volume ( SV) and cardiac output ( CO) were calculated. On the 4th week, HE and Masson′s Trichrome stains were performed. Mann?Whitney u test and non?parametric Wilcoxon test were used. Results (1) As evaluated by PET in the 1st week, the MSI and summed MSI in MSCs group were less than those in control group ( 22. 10 ± 3. 18 vs 35. 70 ± 3. 02, z=-2. 65; 1 013. 50 ± 29. 37 vs 1 084. 00 ± 21?15, z=-1.97;both P<0.05) . Compared to the minimum MSI and summed MSI in the 1st week, those in MSCs group increased significantly (34.00±4.25, z=-2.81;1 075.50±28.30, z=-2.80;both P<0?01) in the 4th week. SRS and SRS% decreased in the 4th week compared to those in the 1st week (20.20±2.24 vs 23.80±1.58, (29.80±3.31)% vs (35.10±2.34)%;both z=-2.08, both P<0.05). The averaged MSI in left ventricular infarction area (MSI<70) also increased (56.25±3.54 vs 48.14±2.71;z=-2.80, P<0.01). The a?bove?mentioned parameters had no statistically significant differences in the 4th week compared to those in the 1st week in the control group (all P>0.05). (2) In the 1st week, the perfusion variables had no signifi?cant differences between the two groups ( P>0.05) . There was no significant difference in any perfusion vari?ables between the 1st and 4th weeks in the two groups, respectively (P>0.05). (3) As evaluated by MRI, the cardiac functional parameters had no significant differences between the two groups at the 1st week. In the MSCs groups, LVEF increased significantly ((54.41±2.62)% vs (47.54±2.43)%;z=-2.60, P<0.01) and ESV reduced significantly ((22.85±1.91) vs (27.07±1.67) ml;z=-2.70, P<0.01) in the 4th week com?pared to those in the 1st week; SV and cardiac CO in the 4th week also increased significantly ((29.35± 1?84) vs (26.52±1.46) ml, (2.23±0.14) vs (1.96±0.13) L/min;z=-2.09 and -1.99, both P<0?05). In the control group, there were no significant differences in the cardiac functional parameters between the 1st and 4th weeks ( all P>0.05) . Conclusions Four weeks after MSCs transplantation for AMI, cardiac func?tion and myocardial glucose metabolism improved significantly but without significant myocardial perfusion improvement. Therefore, the cardiac function improvement might be associated with increased myocardial glucose metabolism.

Objective To investigate the ability of magnetic resonance imaging (MRI) in tracking magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model.Methods Adult Chinese mini-pigs (n = 6) were subjected to open-chest experimental MI operation.Their antegeneic bone marrow-derived mesenchymal stem cells ( MSCs ) was cultured and doubly labeled with ferumoxides and DAPL On the 14 th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). Then the labeled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At 24 hrs and 3 weeks after injection, the contrast and the volume of the MR-MSCs hypointense lesion from the MR images were acquired, and the contrast was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region.After humane euthanasia, the heart was excised and histology corresponding to MRI slices that demonstrated MR-MSCs lesions was performed.Repeated-measures ANOVA and a paired t test were used for comparison of the contrast and the volume of the MR-MSCs hypointense lesion at different time points. Comparisons between independent groups were performed with the standard Student t test.Results The labeling efficiency of ferumoxides and DAPI was 100% . On the 14 th day after the MI operation, the average percentage of infracted myocardial area was (33.6±8.9)% .Twenty- four hours after MSCs transplantation, MSCs injection sites appeared as ovoid hypointensive lesions with sharp border on T2 * images. At 24 h after injection, the signal contrast [(67.00±5.48)% vs (61.92 ±7.76)%,t = 1.65,P =0.1158] and the size [(0.56 ±0.24) cm2 vs (0.52 ± 0.25 ) cm2, t = 0.39, P = 0.7044 ] of the lesions showed no statistical difference between the peri infarct zone and the normal myocardium.At 3 weeks after injection, the signal contrast decreased and the size diminished both in the peri-infarct zone and in the normal myocardium. Moreover, the contrast of the lesions in peri-infarct zone decreased more significantly than that in normal myocardium [(26.88 +7.27)%vs (15.00 :t:4.51)%, F =20.08, P =0.0003].Post mortem analysis found the fluorescontly labeled MSCs demonstrated on histological sections.There were much more dense fluorescently labled MSCs per high power fields at injection sites of normal myocardium than at injection sites of peri-infarct zone [ (106 ±25 )/HPF vs ( 143 ± 31 )/HPF, t = - 2.47, P = 0.0293 ].In MSCs injection sites of the peri-infarct zone,the capillary density was significantly higher than that in control sites [ (13.4 ± 4.0 )/HPF vs (9.4 ±3.1 )/HPF, t = 2.49, P = 0.0229].At 3 weeks after injection, ferumoxide was contained within partial original MSCs.Conclusion Magnetic resonance imaging of MSCs is a feasible method for the in vivo tracking of transplanted stem cells and could reflect the tendency of the local stem cell quantity, but there still has limitation for the semi-quantitation of the transplanted stem cells.

To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract.

AIM: To investigate effects of different therapeutic methods and typical recipes on activation of ERK1/2 in Kupffer cells of rats with fatty liver.METHODS: The rat model of fatty liver was established by feeding high fat diet combinated with distillate spirit.Meanwhile Chinese medicines Shugan fang,Jianpi fang,Huoxue fang,Qushi fang,and Zonghe fang were given to treat different groups respectively.12 weeks later,the Kupffer cells were isolated from livers of control group,model group and different treatment groups by sequential in situ perfusion with collagenaseⅣ and pronase E,density gradient centrifugation,selective adherence.The expression of total ERK1/2 and phospho-ERK1/2 in Kupffer cells of control group,model group and different treatment groups were detected by Western blotting.RESULTS: The expressions of total ERK1/2 and phospho-ERK1/2 were higher in Kupffer cells from model group than those in control group(P

Background::Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods::In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF. Results::We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion::We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.

Micronutrient (MN) deficiency is common in many acute and chronic diseases and should be monitored and managed. In February 2022, the European Society for Clinical Nutrition and Metabolism (ESPEN) released the MN guidelines. This guideline aimed to inform the evaluation, monitoring and treatment principles in MN management as part of daily clinical nutrition practice with standardized terminology to avoid confusion. Extensive literature review was conducted covering multiple databases including Medline, PubMed, Cochrane, Google Scholar, and CINAHL databases. For each kind of MN, information was summarized concerning main functions, optimal detection methods, susceptibility to inflammation, potential toxicity and recommended dose for supplementation via enteral or parenteral nutrition. Practical recommendations on MN supplementation and monitoring were provided to manage MN deficiency in high-risk diseases. This review was based on the contents in the guidelines with an emphasis on interpreting the critical issues.

OBJECTIVETo evaluate the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for myocardial viability.

METHODSTen male miniswines underwent left ventriculography and coronary angiography, followed by stenosis of the left circumflex coronary artery (LCX) using ameroid constrictor. More than one month later, left ventriculography and coronary angiography were performed again, followed by cine-MRI at rest and during stress with incremental dose of dobutamine 5 - 20 micro g.kg(-1).min(-1). Traditional and/or breath-hold cine-MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short-axis tomograms. Regional wall motion score index (WMSI) was calculated. The miniswines were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) delineated myocardial infarction. Microscopy was used to identify myocardial cellular changes.

RESULTSOne pig died, one pig suffered from aneurysm and another showed no negative findings. The other seven pigs were found with hypokinetic (n = 4) or akinetic (n = 3) myocardial regions related to stenosed LCX. Their mean WMSI at rest for the lateral and posteroinferior walls (ischemic regions) of the left ventricle was 2.27 +/- 0.32, as compared with 1.00 +/- 0.00 (P < 0.01) for the corresponding nonischemic anteroseptal regions. Further, the mean WMSI for the ischemic regions was 2.27 +/- 0.32 at rest compared with 1.40 +/- 0.39 (P < 0.01) at the dose of dobutamine 5 micro g.kg(-1).min(-1). However, the mean WMSI at the doses of dobutamine 10 and 20 micro g.kg(-1). min(-1) were 1.70 +/- 0.76 and 1.75 +/- 0.83, respectively, with no significant difference as compared with the mean WSCI at rest (P > 0.05). The pathologic examination showed viable myocardium at the ischemic regions.

CONCLUSIONLow-dose dobutamine (5 micro g.kg(-1).min(-1)) recovers hypokinetic or akinetic myocardial regions, and dobutamine stress MRI can be used to detect myocardial viability.

Objective To establish the chronic low flow myocardial hibernation animal model in pigs, and to assess the diagnostic value for myocardial hibernation by using various imaging methods. Methods A total of 13 miniswine (30-40 kg) were used. All animals underwent general anesthesia and orotracheal intubation while the animals were mechanically ventilated. Under sterile conditions, left ventriculography and coronary angiography were performed by introduction of catheter into the right femoral artery. Further, a left anterolateral thoracotomy was performed in the third intercostal space. The proximal LCX was dissected free to allow placement of an ameroid constrictor. More than 1 month later, left ventriculography and coronary angiography were performed again, followed by cine MRI at rest and during stress with low dose of dobutamine (5 ?g?kg -1 ?min -1 ), respectively. Traditional and/or breath hold cine MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short axis tomograms. Regional wall motion score index (WMSI) was calculated. At the same time 99m Tc MIBI myocardial SPECT was performed at rest and during nitroglycerin administration, respectively. All animals were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) staining was used to assess the myocardial infarction. Electron microscopy was used to identify myocardial cellular changes characteristic of hibernating myocardium. Results Three pigs died during surgery or within two weeks after surgery. One pig died of anesthesia during SPECT examination, 1 pig suffered from aneurysm, and another one pig showed negative findings. The other 7 pigs were found with hypokinetic ( n =4) or akinetic ( n =3) myocardial regions related to stenosed LCX (70%-99%). Resting cine MRI demonstrated decreased regional motion of the lateral and posteroinferior walls (ischemic regions) of the left ventricle ( n =7), compared with the nonischemic anteroseptal regions; but the low dose dobutamine (5 ?g?kg -1 ?min -1 ) could recover those hypokinetic or akinetic myocardial regions, characteristic of hibernating myocardium. Resting 99m Tc MIBI myocardial SPECT ( n =6) showed a fixed perfusion defect on the corresponding ischemic areas, which became reversible on the nitrate augmented myocardial perfusion imaging. It also indicated myocardial viability presented at the ischemic areas. TTC staining revealed patchy infarction of the area at risk localized to the endocardial surface ( n =3), and no myocardial infarction ( n =4). Electron microscopy of sections from the hibernating regions revealed loss of contractile materials, increased numbers of small mitochondria, and glycogen accumulation within viable cardiomyocytes, which had been described as hallmarks of hibernating myocardium. Conclusion Chronic low flow myocardial hibernation can be reproduced in an animal model during progressive coronary stenosis caused by ameroid constrictor.