PBL is problem-based and student-centered learning pattern. PBL has been proved to be an effective teaching,which is helpful to improving the students’learning enthusiasm and learning efficiency,and to training their clinic thoughts and the capability of teamwork.

Objective To study whether the uremic toxins accumulated long-term in uremia patients may be involved in oxidation of protein by forming advanced oxidative protein products (AOPPs). Methods Malonylaldehyde (MDA), hippuric acid (HA) and p-cresol were used as the representatives of uremic toxins. Human albumin serum (HSA), plasma specimens from normal or uremia patients were incubated respectively with MDA (10 retool/L), HA (20 mmol/L) and p-cresol (10 retool/L) or PBS (20 retool/L, pH 7.4, as control groups) at 37℃ for 30 minutes or 24 hours, respectively. Those indices such as AOPPs, protein thiol groups (Pt-SH) and dityrosine were used as biomarkers of protein injury. High performance liquid chromatography (HPLC) was employed to identify the aggregation and cross-links of modified proteins. Results AOPPs levels in all groups containing poison compounds were significantly increased by 121.5%(P<0.05) compared to that in control groups. Uremic toxins also resulted in over 14.7% loss in Pt-SH (P< 0.05) and 119.2% increment in dityrosine, respectively (P<0.05). Meanwhile, the formation of HMW-AOPPs in a time-dependent manner was observed by HPLC and cross-linked protein levels were significantly increased by 148.45%～333.3% in comparison with control groups. Conclusion Uremic toxins can directly mediate the damage of proteins by inducing the formation of HMW- AOPPs in a time-dependent manner, which is also one of the mechanism of AOPPs production in vivo besides the activation of the myeloperoxidase-H2O2-Cl pathway.

Objective To investigate the protective effects of ethanol extracts of Tadehagi triquetrum ( TTOE) on car-bon tetrachloride ( CCl4 )-induced acute liver injury in mice. Methods Kunming mice were randomly divided into six groups:normal control group ( NC group) ,model control group,bifendate dropping pill group,low-,medium-and high-dose TTOE groups. The liver injury model was established by administration of CCl4 in all the groups except the NC group.The indexes of the liver, spleen and thymus were obtained.The activities of serum ALT,AST,ALP,LDH, albumin and T-AOC were measured.The activi-ties of SOD and GSH-PX and the contents of MDA,NO and GSH and Cyt P450 were also detected in hepatic tissues. Results TTOE at different doses could obviously reduce the indexes of the liver,thymus and spleen,which were (57.13±0.71),(32.44± 0.24),and (27.78±0.16),respectively,in high-dose TTOE group,and there were significant differences between the TTOE groups and model control group (P<0.01).The activities of ALT,AST,ALP and LDH were obviously decreased in high-dose TTOE groups,which were (65.59±8.23),(141.38±15.52),(2 462.4±253.6),(172.51±20.64),respectively,in the TTOE high-dose group (P<0.01).The serum levels of Alb and T-AOC were obviously increased,the contents of NO and MDA significantly decreased and the activities of SOD and GSH-PX and the contents of GSH Cyt P450 in liver tissues profoundly increased in TTOE groups when compared with those in model control group ( P<0.05 or P<0.01) . Conclusion TTOE could protect against acute hepatic injury induced by CCl4 in mice,which may be associated with the decrease in the activities of liver enzymes,anti-oxide free radical effect,decreased NO content and inhibited lipid peroxidation.

Objective To study the effects of oxidants on the structure of albumin. Methods Using both AOPPs and protein carbonyl content as indices. The oxidative stress level in normal controls and uremia patients was evaluated. Albumin in plasma was purified by HPLC and then was subjected to amino acids composition assay. Results Both AOPPs level and protein carbonyl content in uremic patients were significantly higher than those in controls (P

Objective To study the effect of oxidative modification of hydrochlorous acid (HOCl) on human serum albumin (HSA) and the relationship between the AOPPs and HOCl-treated HSA. Methods Purified HSA (60 mg/ml) was treated with HOCl (0, 1, 5, 10, 20, 30, 40, 50 and 60 mmol/L). Size-exclusion chromatography was applied to estimate molecular weights of oxidized products of HSA by HOCl and spectrum scan from 190 nm -400 nm was performed to observe the spectrum characteristics of all variants of HSA. Results Major products of HSA after exposure to HOC1 were dimer and hexmer of HSA. The first-order process could be employed to describe the oxidative dynamics of monomer and dimer of HSA oxidized by HOCl. To AOPPs formation mediated by oxidant was identified as pseudo first-order reaction. However, formation hexmer was much in accordance with second-order reaction. Hexmer was also a major contributor to AOPPs in all types of modified HSA. Spectral analysis showed that red shift of absorbance maximum of polymers of HSA occurred, suggesting that a possibility that polymers of HSA were cross linked by tyrosine residues in protein. Conclusions Protein aggregation is primary consequence of HSA after its exposure to HOCl. Hexmer of HSA is the major contributor to AOPPs.

This article was to elucidate that the needling depth is closely related to the meridian qi, disease location, disease nature and needled area based on the records of needling depth in Nei Jing (Canon of Internal Medicine). Moreover, different depths will produce different therapeutic efficacies;meanwhile, improper depth may lead to grave consequences.

In recent years, there has been an increasing trend regarding the incidence of anaphylaxis among children in China. Despite the existence of relevant diagnosis and treatment guidelines for regulation, due to reasons such as uneven allocation of medical resources, there are still many problems in the specific implementation process of primary health care institutions, and these problems may lead to untimely and irregular handling of allergic reactions, thereby increasing the risk for pediatric patients. This review discussed the related issues existing about the diagnosis and treatment of anaphylaxis in children in primary health care institutions.

Objective To establish the SD rat aortic dissection(AD)model by using both BAPN and AngⅡ,in order to investigate AD's pathogenesis. Methods 90 three weeks old SD rats were equally divided into three groups randomly:control group,medicine gavage group and blank medicine gavage group. Rats in control group were fed on a regular diet;BAPN ( 1g/ kg per day)was forced into rats'stomach in the medicine gavage group;the same volume saline was forced into rats' stomach in the blank medicine gavage group. 4 weeks later,when the rats were 7 weeks old,we stopped giving them BAPN, but to implant an omicro-osmotic pump subcutaneously in the abdomen. The pumps in control group and blank medicine gavage group were filled with 0. 9％ saline,the medicine gavage group'pumps were filled with AngⅡsolution( 1 μg·kg- 1 ·min- 1 ). 1 week later,all the survivals were dissected after anesthesia and the aortic vessels were acquired. All the acquired aortic ves-sels were proceed pathological examination. All the rats dead during the process of the experiment were dissected immediately to get the aortic vessels and proceed pathological examination. Results All rats in control group and blank medicine gavage group were survival,there was no aortic dissection or death. In medicine gavage group, 15 rats developped aortic dissection, 12 a-mong them were died of aortic dissection rupture,the aortic dissection formation rate was 50％ . Conclusion Using BAPN and AngⅡ to establish the SD rat AD model is feasible,it is simple and practicable,meanwhile,it has high aortic dissection for-mation rate. The process is similar with human's aortic dissection process.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

Objective To explore the regulatory effect of miR-6838-5p on DDR1 gene expression and proliferation of breast cancer cells.Methods The expression levels of miR-6838-5p in normal breast epithelial cells and breast cancer cells were detected using qRT-PCR,and the potential target genes of miR-6838-5p was predicted using TargetscanV 8.0.Double luciferase reporter gene experiment was performed to verify the binding between miR-6838-5p and DDR1.Breast cancer MCF-7 cells were transfected via liposome,miR-6838-5p mimic,miR-6838-5p inhibitor,DDR1 siRNA,DDR1-overexpresisng vector,or both miR-6838-5p mimic and DDR1-overexpressing vector,and the changes in cell proliferation were examined with CCK-8 and EdU assays;Western blotting was used to detect the expression of DDR1.The mediating role of DDR1 in miR-6838-5p overexpression-induced inhibition of MCF-7 cell proliferation was verified in a nude mouse model bearing MCF-7 cell xenografts.Results The expression of miR-6838-5p was significantly lower in breast cancer cells than in normal breast epithelial cells.In MCF-7 cells,miR-6838-5p overexpression induced significant inhibition of cell proliferation.Dual luciferase reporter gene experiment demonstrated a binding relationship between miR-6838-5p and DDR1(P<0.01).Western blotting showed that miR-6838-5p overexpression significantly lowered DDR1 expression in MCF-7 cells,and DDR1 overexpression promoted proliferation of the cells;co-transfection of the cells with DDR1-overexpressing vector significantly attenuated the inhibitory effect of miR-6838-5p mimic on cell proliferation.In the tumor-bearing nude mice,the xenografts overexpressing miR-6838-5p showed a significantly smaller volum with obviously the expression of DDR1.Conclusion Overexpression of miR-6838-5p inhibits breast cancer cell proliferation by regulating DDR1 expression.