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.

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 explore the effect and mechanism of microRNA (miR)-155-5p on myocardial pyroptosis in rats with myocardial ischemia-reperfusion injury (IRI). Methods Sixty SD rats were randomly divided into sham group, IRI group, agomir-NC group, miR-155-5p agomir group, antagomir-NC group, and miR-155-5p antagomir group, with 10 rats in each group. Echocardiography was used to measure the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) of rats. Enzyme-linked immune absorbent assay (ELISA) was used to detect the levels of creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) in serum, as well as the levels of interleukin (IL)-1β, IL-6, IL-18, and tumor necrosis factor (TNF)-α in myocardial tissue of rats. Hematoxylin-eosin staining was used to observe pathological changes in rat myocardial tissue. Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of miR-155-5p and silent information regulator 1 (SIRT1) messenger RNA (mRNA) in myocardial tissue of rats. Dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-155-5p and SIRT1. Western blot was used to detect the expression levels of SIRT1, NOD-like receptor protein 3 (NLRP3), cleaved cysteine aspartate specific proteinase-1 (Cleaved Caspase-1), and gasdermin D (GSDMD) proteins in myocardial tissue of rats. Results Compared with the sham group, the LVEDD and LVESD of rats in the IRI group were increased, LVEF and LVFS were decreased, serum levels of CK-MB, LDH, and cTnT were increased, IL-1β, IL-6, IL-18 and TNF-α levels in myocardial tissue were increased, myocardial tissue structure was severely damaged, myocardial fibers were disordered, relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased, and the relative expression of SIRT1 protein was decreased (all P<0.05/5). Compared with the IRI group, the rats in the miR-155-5p agomir group had increased LVEDD and LVESD, decreased LVEF and LVFS, increased serum levels of CK-MB, LDH, and cTnT, increased myocardial tissue levels of IL-1β, IL-6, IL-18, TNF-α, aggravated myocardial tissue lesions, increased relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins, and decreased relative expression of SIRT1 protein, and the rats in the miR-155-5p antagomir group had decreased LVEDD and LVESD, increased LVEF and LVFS, decreased serum levels of CK-MB, LDH, and cTnT, decreased myocardial tissue levels of IL-1β, IL-6, IL-18, TNF-α, reduced myocardial tissue lesions, decreased relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins, and increased relative expression of SIRT1 protein (all P<0.05/5). miR-155-5p was negatively correlated with the expression levels of SIRT1 in rat myocardial tissue, and SIRT1 was a target gene of miR-155-5p. Conclusions miR-155-5p may participate in the regulation of myocardial IRI in rats by targeting the downregulation of SIRT1 and promoting NLRP3-mediated myocardial pyroptosis.

Objective To observe the levels of four bisphenols (bisphenol A,B,S and F) and their correlation with renal function in chronic kidney disease (CKD) patients.Methods Patients with CKD were identified according to Kidney Disease:Improving Global Outcomes (KDIGO) criteria.Sixty-three CKD patients and eleven healthy controls were enrolled.CKD patients were further classified as mild renal injury group (CKD stage 1 and 2,n=30),moderate renal injury group (CKD stage 3,n=19) and severe renal injury group (CKD stage 4 and 5,n=14).The levels of four bisphenols in serum were determined by high performance liquid chromatography (HPLC).The correlation between concentrations of four bisphenols and estimated glomerular filtration rate (eGFR) was assessed by Spearman's rank correlation analysis.The associations of four bisphenols with coronary heart disease,diabetes and hypertension in CKD patients were estimated by binary multivariate logistic regression.Results (1) Four bisphenols were not detected in serum of healthy control.In the mild renal injury group the bisphenol A and bisphenol S were not detected,and patients had 5.24 (5.24,9.38) μg/L bisphenol B and 0.74 (0.74,0.74) μg/L bisphenol F.In the moderate renal injury group bisphenol S was not detected,and patients had 2.79 (1.01,4.53) μg/L bisphenol A,5.24 (5.24,5.24) μg/L bisphenol B and 0.74 (0.74,0.74) μg/L bisphenol F.In severe renal injury group patients had 14.30 (7.97,18.17) μg/L bisphenol A,0 μg/L bisphenol B,23.73 (23.73,136.59) μg/L bisphenol S and 0.74 (0.74,1.42) μg/L bisphenol F.The levels of bisphenol A and bisphenol S in severe renal injury group were higher than those in the healthy control group,mild renal injury group and moderate renal injury group (all P ＜ 0.05).Bisphenol B and bisphenol F were not statistically different among four groups.(2) Bisphenol A and bisphenol S were negatively correlated with eGFR (r=-0.779,P ＜ 0.001;r=-0.546,P ＜ 0.001).(3) Among CKD patients,bisphenol A was correlated with diabetes (OR=4.951,95％CI 1.603-15.294,P=0.005),and bisphenol S was correlated with hypertension (OR=4.466,95％ CI 1.575-12.666,P=0.005).Conclusions CKD patients have a variety of bisphenol compounds,especially bisphenol A and bisphenol S.Bisphenol A and bisphenol S have high levels,and their exposures are correlated with renal function.

OBJECTIVE To provid e reference and sugge stions for improving the volume-based procurement of drugs and medical consumables （hereinafter referred to as “consumables”）in China. METHODS The relevant policy documents of centralized volume-based procurement of drugs and consumables published from November 2018 to November 2021 were retrieved ； the implementation status and problems of centralized volume-based procurement of drugs and consumables in China were analyzed by using the policy analysis method and referring to relevant research literatures. RESULTS & CONCLUSIONS National health department and healthcare security administration guaranted the rational use of selected products in medical institutions through incentive and supervision measures ；healthcare security administration should optimize the way of medical insurance payment ， promote the medical institutions to control the fees by themselves ，and conduct the credit evaluation of bidding and procurement ； medical products administration should evaluate the consistency of drugs and supervise the quality of selected products. With the normalization of centralized volume-based procurement of drugs and consumables organized by the state and trans-regional alliance ， the drug varieties and dosage forms included in centralized procurement were increasingly in line with the demand of Chinese pharmaceutical market. The price of most selected drugs decreased by more than 50％，and the decrease of consumables was significantly higher than that of drugs. The selected enterprises were mainly domestic generic drug enterprises ，and domestic consumables had gradually become the competitors and substitute of imported consumables. However ，there were still some problems such as repeated bidding and procurement in various alliances and provinces （autonomous regions and municipalities ）， unclear construction of compensation mechanism in medical institutions ，inconsistent bidding and procurement rules and quality evaluation standards for consumables ，low localization rate of some consumables ，low innovation level and profitability of pharmaceutical enterprises and consumables manufacturers. Local centralized volume-based procurement should be encouraged ，and the bidding and procurement rules and quality evaluation standards of “one product ，one policy ”should be gradually established. Great importance should be paid to the construction of compensation mechanism of medical institutions ，standardize zhangqiuyu739632@126.com the dynamic adjustment of medical serv ice prices ；pharma- ceutical enterprises and consumables manufacturers should increase research and development investment to transform into innovative and diversified enterprises ，so as to improve the competitiveness of domestic drugs and consumables.