OBJECTIVE To analyze the use status and development trend of proton pump inhibitors(PPIs) in 33 hospitals in Wuhan, Hubei Province after the implementation of the national centralized drug procurement(NCDP) policy, and to provide reference for promoting the subsequent rational use of NCDP drugs and improving related policies. METHODS To make statistics and analysis of purchasing amount of PPIs, defined daily dose system(DDDs), defined daily dose consumption(DDDc) and utilization rate of 33 hospitals in Wuhan in 2019 and 2022. RESULTS After the implementation of the NCDP policy, the total purchasing amount of PPIs decreased by 53.6%, DDDs decreased by 15.4%, DDDc decreased by 45.2%, and the utilization rate of PPIs injectable dosage forms decreased by 12.6%. After NCDP, the highest growth rate of oral dosage forms was omeprazole(5.7%), followed by rabeprazole(5.0%), while injectable dosage forms showed a significant difference in utilization rate, with a significant decline in NCDP varieties and a significant increase in non-NCDP varieties. The overall NCDP utilization rate of PPIs in Wuhan was 64.9%, with little difference among hospitals of different grades. CONCLUSION The NCDP policy achieves the purpose of reducing the drug cost of patients and improving the accessibility of drugs, and is more optimized in the selection of dosage forms, which is in line with the policy expectations overall; but the quantity and price of PPIs in Wuhan decreased after NCDP, and highlighted a certain tendency in the selection of varieties. In the future, we still need to optimize measures to guide clinical priority in the selection of NCDP drugs, to ensure and improve the implementation of NCDP policy.

Objective To study the two-phase flow dynamics distribution and red blood cell distribution under the fluid-solid coupling interaction in left coronary artery at the typical time point within one cardiac cycle,and to investigate the formation and development mechanisms of left coronary artery atherosclerotic plaque Methods The blood was regarded as a two-phase fluid.Based on fluid-solid interaction between blood and vascular wall,the computational fluid dynamics method was used to make the transient numerical simulation of two-phase flow in the left coronary artery under fluid-solid interaction;the distribution of blood flow in the left coronary artery at the typical time point within one cardiac cycle was studied,the relationship between hemodynamic parameters and the formation of atherosclerotic plaque was analyzed.Results A lowspeed eddy zone existed in an area between the distal segment of circumferential branch and the proximal outside of blunt-edge branch of the left coronary artery,where both internal wall shear stress and red blood cell volume fraction were very small and the blood flow pattern was very complicated.Conclusion At the lowspeed eddy zone that carries small wall shear stress,the lipid concentration polarization and macromolecular material deposition are easy to be produced.The area that has less red blood cells is liable to develop hypoxia,resulting in increased vascular wall permeability and intimal injury,which will activate the immune system,causing lipid accumulation in vascular wall and intimal hyperplasia and,thus,to induce the formation of atherosclerotic plaque.(J Intervent Radiol,2017,26:253-257)

Aim To explore the role of endoplasmic reticulum stress(ERS) in Astragaloside Ⅳ-induced cardioprotection in H9c2 cardiac cells, and to explore the potential mitochondrial mechanism.Methods Conventional culture was performed of rat heart tissue-derived H9c2 cells.Experiment was randomly divided into the control group, the ERS inducer 2-Deoxy-D-Glucose(2-DG) group, Astragaloside Ⅳ and 2-DG combination group, Astragaloside Ⅳ group.Confocal microscopy was used to observe the changes of TMRE fluorescence intensity so as to confirm the influence of ERS on the mitochondrial potential, and further speculate on the opening of the mitochondrial permeability transition pore(mPTP).Western blot analysis was applied to detect the expressions of ERS proteins GRP 78, GRP 94 and IRE1.Transmission electron microscopy was used to observe the ultrastructure of the cells.Results Different doses of 2-DG could mimic the mPTP opener atractyloside to induce the mPTP opening with the peak at 100 μmol·L-1;Astragaloside Ⅳ significantly reduced 2-DG-induced mPTP opening, the expression of GPR 78, GRP 94 and IRE1 and reduced injury of mitochondria and endoplasmic reticulum.Conclusions Endoplasmic reticulum stress could be induced by 2-DG.Astragaloside ⅳ-induced mitochondrial cardioprotection involves inhibition of the ERS through GRP 78, GRP 94 and IRE1 by prevention of the mPTP opening.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

Objective To study the distribution of hemodynamics in carotid artery under the fluid-solid interaction at the typical point of time during a single cardiac cycle, and to explore the mechanism of the formation and development of carotid atherosclerotic plaque. Methods Numerical analysis the blood flow characteristics within a cardiac cycle in carotid artery was analyzed by using computational method of fluid dynamics. Based on the hemodynamic parameters, the influences of the cardiac systole and diastole on the blood flow distribution were analyzed. Results The distribution of blood flow in the carotid artery within a typical cardiac cycle was obtained. Compared with the findings in cardiac diastole, a larger area of blood stasis at the entrance of external carotid artery was observed. In this area, the flow velocity, the wall pressure and the wall shear stress were all lower, while the arterial wall deformation and von Mises equivalent stress were larger. Conclusion Under fluid-solid interaction, the low blood flow in carotid artery causes blood reflux, resulting in the deposition of lipid, fiber and other large molecular materials. The low wall pressure produced“negative pressure” effect, thus the normal blood flow is changed, the flow velocity becomes slow, and the blood supply of the brain becomes insufficient. The low wall shear stress destroys the blood flow near the wall, causing the increase of platelet activity and intimal hyperplasia. The larger arterial wall deformation variable and von Mises equivalent stress can cause stress concentration and increase vascular rupture risk.

Objective To compare the rates of clearance of different solutes during continuous veno-venous haemodiafiltration (CVVHDF) between pre-dilution and post-dilution.Methods A study in vitro was carried out using model CRRT system with AN69 filter used,which was applied to perform CVVHDF for solutes clearance.The removed amounts of different solutes including potassium ion (K +),creatinine (Cr),vancomycin,insulin,and interleukin-6 (IL-6) were determined in the groups of control (without dilution),pre-dilution and post-dilution during CVVHDF at the same substitution fluid amount.Each group was repeated 4 times (n =4).Results Post-dilution mode increased K +,Cr,vancomycin and insulin clearances significantly.There was no difference in clearance of IL-6 between the pre-and post-dilution groups.In the control group,insulin and IL-6 levels were decreased extremely.Conclusions In general,the rate of clearance using post-dilution of CVVHDF is higher than that using pre-dilution.Among high molecular weight solutes,the difference in clearance is not significant.The control group demonstrates insulin and IL-6 adsorbed by the filter.

Objective To evaluate the short-term efficacy of lamivudine versus entecavir for patients with HBeAg-negative acute-on-chronic liver failure (ACLF) with different pretreatment liver failure degrees.MethodsA total of patients with HBeAg-negative ACLF were enrolled into this retrospective study.Seventy-two cases were treated with lamivudine 100 mg daily,while 93 cases were treated with entecavir 0.5 mg daily.Biochemical items,model for end-stage liver disease (MELD)score,hepatitis B virus (HBV) DNA level and mortality were observed.The efficacies of the two drugs were analyzed in patients with different degrees of liver failure.The comparison of rates was done using chi-square test and the measurement data were compared by t test.ResultsAmong the patients with pretreatment MELD scores above 30,the post-treatment HBV DNA levels in lamivudine group and entecavir group were (3.6 ± 1.1) lg copy/mL and (3.7 ± 1.4) lg copy/mL,respectively (t=0.181,P=0.859) and the mortalities were 92.0％ and 91.8％,respectively (χ2 =0.002,P=0.680).For the patients with pretreatment MELD scores from 23 to 30,the post-treatment HBV DNA levels in two groups were (3.2± 1.1) lg copy/mL and (3.2±2.3) lg copy/mL,respectively (t=0.760,P=0.455) and the mortalities were 42.9％,54.1％,respectively (χ2 =0.799,P=0.455).In patients with pretreatment MELD scores below 23,the post-treatment HBV DNA levels in two groups were (3.1±1.0) lg copy/mL and (2.8±1.5) lg copy/mL,respectively (t=-0.740,P=0.464) and the mortalities were 3/19 and 6.3％,respectively (χ2=1.227,P=0.455).In lamivudine group,the mortalities were significantly different among patients with three different ranges of pretreatment MELD scores (χ2 =26.967,P =0.000).The similar differences were also found in entecavir group (χ2 =41.260,P=0.000).ConclusionsAmong treatment na?ve patients with HBeAg-negative ACLF,the short-term efficacy of lamivudine versus entecavir is equal if the degree of pretreatment liver failure is similar.Meanwhile,the degrees of pretreatment liver failure significantly affects the outcome of the treatment.

Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P＜0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P＜0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.

Objective To investigate the risk factors of hepatitis B virus(HBV) re-infection after orthotopic liver transplantation(OLT)and to evaluate the therapeutic efficacy of hepatitis B immunoglobulin(HBIG)combined with nucleos(t)ide analogues. Methods The study included 160 patients with HBVrelated liver diseases who underwent OLT in the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to Augest 2007, 117 of whom were treated with nucleos(t)ide analogues before OLT;and all patients were received HBIG i. m and nucleos(t)ide analogues treatment after OLT. Preoperative data of the patients were retrospectively reviewed, and HBV re-infection was assessed prospectively. Independent t test was used to compare normally distributed data and Fisher's exact test was used for the comparison of rates among groups. Results HBV re-infection Was observed in 19 patients after OLT with a rate of 11. 88%(19/160), which was not correlated with HBV DNA loads, HBeAg and the duration of antiviral therapy before OLT(r=0.108, 0.127 and 0.033, P>0.05). Of 19 patients with HBV re-infection, 17 were treated with lamivudine after OLT, and HBV YMDD mutants were detected in 8. The YMDD positive group had a higher HBV DNA level than YMDD negative group(7.0 ± 2.0 log copies/mL vs 3.2 ± 2.5 log copies/mL, t = 3.531, P=0.003). Among above 17 patients, 12 received adefovir add-on treatment, and3 received entecavir instead of lamivadine; all achieved satisfactory responses. Conclusions Low dose of HBIG combined with long-term use of nucleos(t)ide analogues can effectively prevent HBV re-infection after OLT. HBV YMDD mutation may be the primary reason for HBV re-infection in the patients treated with lamivudine after OLT.

Objective To evaluate the long-term prognosis of patients with HBV-related decompensated cirrhosis after treatment with nucleos (t) ide analogues. Methods Totally 94 patients with HBV-related decompensated cirrhosis were enrolled, 53 in nucleos(t) ide group, 41 in control group, and both received routine treatments. Patients in nucleos (t)ide analogue group also received lamivudine ( 100 mg/d), or adefovir ( 10 mg/d), or entecavir (0.5 rag/d). The follow-up was terminated for those who developed hepatocellular carcinoma, received liver transplantation, died or refused the treatment. Serum biochemical markers, Child-Pugh grades and clinical outcomes were compared between two groups at the end of following up. Results After nucleos (t) ide analogues therapy, ALT, AST, globulin ( Glb), and TBil decreased, while Alb and cholinesterase (CHE) increased in the nucleos(t)ide group, and Chiid-Pugh scores decreased in 43 (81.1%) patients. While in the control group, ALT, AST, Glb and TBil did not show significant changes, but the CHE was significantly lower than before ( t = 5. 225, P < 0. 01 ). More patients in nucleos (t)ide group showed improvements in Child-Pugh grades, and there was significant difference between the two groups (X2 = 52.16, P <0.01). The incidence of HCC is lower in nucleos(t) ide group (0%) than that in the control group ( 19.5% ) ( X2 = 23.07, P < 0.01 ). The incidence of death and liver transplantation between two groups did not show siguificant difference. Conclusions Nucleos(t) ide analogues therapy can significantly improve biochemical status of liver functions in patients with HBV-related decompensated cirrhosis. The incidence of hepatocellular carcinoma may decline and the long-term prognosis can be improved.