Exhaustion of CD8 T cell immune functions in spleen of mice with different doses of Echinococcus multilocularis infections / 中国血吸虫病防治杂志

ObjectiveTo examine the changes in the immune functions of CD8+ T cells in the spleen of mice following Echinococcus multilocularis infections at various doses and at different time points. MethodsThe E. multilocularis protoscoleces were collected, and E. multilocularis infection was modeled in mice via the hepatic portal vein at doses of 50 (low-dose), 500 (medium-dose) and 2 000 protoscoleces (high-dose), while physiological saline served as controls. Mouse spleen was isolated 2 (earlystage), 12 (middle-stage) and 24 weeks post-infection (late-stage), and spleen lymphocytes were harvested. The phenotype of memory CD8+ T cells and 2B4 expression were quantified in the mouse spleen, and the secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17A and IL-10 was measured. Results A central-memory phenotype was predominant in the CD8+ T cells in the spleen of mice at the early stage of high-dose protoscolece infections, and the proportion of central-memory CD8+ T cells was significantly greater in the high-dose group than in the control group (35.50% ± 2.00% vs. 25.90% ± 2.46%, P < 0.01), while a effector- memory phenotype was predominant in the CD8+ T cells in the spleen of mice at the late stage of medium- and high-dose protoscolece infections, and the proportions of effector-memory CD8+ T cells were significantly greater in the medium- (25.70% ± 4.12%) and high-dose group (28.40% ± 4.12%) than in the control group (10.50% ± 6.45%) (P < 0.05). The proportions of the central-memory CD8+ T cells were significantly higher in the high-dose group than at middle and late stages than at the early stage (P < 0.01), and the proportion of effector-memory CD8+ T cells was significantly greater in the high-dose group at the late stage than at early and middle stages (P < 0.05). The secretion of IFN-γ and IL-17A by spleen CD8+ T cells was elevated in the low- and medium-dose groups at the early stage of infection, and high-dose protoscolece infection promoted the secretion of IFN-γ and TNF-α by spleen CD8+ T cells; however, the levels of IFN-γ and TNF-α were significantly lower at the late stage than at the early and middle stages (P < 0.05). In addition, high 2B4 expression was detected in spleen CD8+ T cells in the middle- and high-dose groups at the late stage of infection, and the 2B4 expression was significantly higher in the medium(4.73% ± 1.56%) and high-dose groups (4.94% ± 1.90%) than in the low-dose group (2.49% ± 0.58%) and the control group (2.92% ± 0.60%) (P < 0.05). Conclusions E. multilocularis may be killed and eliminated through the host immune responses at the middle and late stages of low- and medium-dose protoscolece infections, while high-dose protoscolece infections may trigger the upregulation of 2B4 expression in mouse spleen CD8+ T cells at the late stage, which leads to immune exhaustion and the resultant chronic infections.

A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China / 中华医学杂志(英文版)

BACKGROUND@#Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions.@*METHODS@#Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses.@*RESULTS@#At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group.@*CONCLUSIONS@#In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov.

Ulnar artery compression: a feasible and effective approach to prevent the radial artery occlusion after coronary intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Radial artery (RA) occlusion (RAO) is not rare in patients undergoing coronary intervention by transradial approach (TRCI). Predictors of and prevention from RAO have not been systematically studied. This study aimed to analyze the risk factors of the weakness of RA pulsation (RAP) and its predictive value for RAO after TRCI, and simultaneously to describe a feasible and effective approach to maintain RA patency.</p><p><b>METHODS</b>Between June 2006 and March 2010, all patients who underwent TRCI were classified according to the weakness of RAP after removing compression bandage with confirmation by Doppler ultrasound for the first 30 consecutive patients. Among a total of 2658 patients studied, 187 (7%) patients having a weaker RAP were prospectively monitored. At 1 h after bandage removal, the ulnar artery in puncture side of all patients was blocked with manual compression to favor brachial and collateral artery blood flow through the RA until a good RAP was restored. The primary analysis was the occurrence of RAO.</p><p><b>RESULTS</b>Doppler ultrasound demonstrated the significant reduction of both systolic velocity (61.24 ± 3.95 cm/s vs. 72.31 ± 3.57 cm/s) and diastolic velocity (1.83 ± 0.32 cm/s vs. 17.77 ± 3.97 cm/s) in RA at access side as compared to the contralateral RA (all P < 0.001), but these velocities in ipsilateral ulnar artery (81.2 ± 2.16 cm/s and 13.1 ± 2.86 cm/s, respectively) increased profoundly. The average time of ulnar artery compression was 4.1 ± 1.2 h (ranged 2.5-6.5 h). There were two patients experienced persistent RAO with a success rate of 98.9% and RAO in 0.075% of patients after ulnar artery compression was applied. The pulsation of the ulnar artery after compression was removed had not been influenced by the compression.</p><p><b>CONCLUSIONS</b>After intervention using TRCI approach, the presence of a weaker RAP is an indicator of imminent RAO. The continuing compression of ipsilateral ulnar artery is an effective approach to maintain RA patency.</p>

Dynamic expression of toll like receptor 2 and 4 in a rat model of myocardial ischemia/reperfusion injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the role of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in myocardial ischemia/reperfusion injury (MI/RI) by observing the dynamic expression changes at mRNA and protein levels early after myocardial ischemia/reperfusion (I/ R).</p><p><b>METHODS</b>The Wistar rats were randomly divided into Sham and I/R group (n = 42), and killed according to different reperfusion time (1, 2, 4, 6, 12, 24 h and 7 d). Structural and morphous changes of myocytes were observed under optical microscope. The mRNA and protein levels of TLR2 and TLR4 were detected using real-time PCR (RT-PCR). Monocyte chemokine protein-1 (MCP-1) and interleukine-6 (IL-6) mRNA levels were measured by reverse transcriptase-polymerase chain reaction (rt-PCR).</p><p><b>RESULTS</b>(1) With the extension of reperfusion time, the myocardial infarct size increased smoothly, and reached the plateau at 4 h, then stayed in the platform. After reperfusion for 7 d, the ventricular had been remodeled. (2) At the beginning of reperfusion, myocardial structure showed no significant change in Sham group, but had different degrees of injury in I/R group. In rats of the group reperfused for 7 d the left ventricular remodeling could be visible. (3) Compared to sham group,TIR2, TLR4, MCP-1, IL-6 mRNA level were increased in myocardium in I/R group. TLR2 and TLR4 both peaked at 4 h of reperfusion, IL6 peaked at 6 h, followed by a gradually decrease. TLR4 and IL-6 mRNA levels rose again at 7 d. MCP-1 level in I/R group remained fairly with sham group at the beginning of reperfusion, and markedly elevated at 7 d.</p><p><b>CONCLUSION</b>Expression of TLRs mRNA in myocardium during early after myocardial ischemia/reperfusion increased rapidly and activated TLRs might play an important role in MI/RI through promoting the generation of inflammatory factors. At the late reperfusion, TLRs levels raise again and the expression of inflammatory factors increase once again, Those may probably affect the remodeling of ventricular, and injure myocardial structure and function.</p>

Correlation between MPO 129 A/G polymorphism and severity of coronary artery disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the relationship between myeloperoxidase (MPO) 129 A/G promoter polymorphisms and the severity of coronary artery disease (CAD).</p><p><b>METHODS</b>The study enrolled 267 patients who had been diagnosed as coronary artery diseases by coronary angiography. The serum MPO activity was detected by colorimetric method. PCR-RFLP method was used to decide the genotypes of the patients. The severity of CAD was evaluated by the numbers of stenotic coronary arteries and the Gensini scores respectively.</p><p><b>RESULTS</b>The MPO 129 locus G and A alleles frequency were 0.893 and 0.107, respectively. No significant difference was observed in serum MPO activity between different genotypes (P > 0.05). The distribution of genotypes in different Gensini score groups had no significant difference (P > 0.05). The patients with GG genotypes were prone to develop mutivessel diseases.</p><p><b>CONCLUSION</b>No significant correlation exists in MPO 129 locus polymorphism and serum MPO activity. The MPO 129 locus polymorphism isn't a reasonable predict factor of CAD severity.</p>

Benefits of placing intra-aortic vacant guide wire on interventional treatment of aorto-ostial lesions / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the potential benefits of placing intra-aortic vacant guide wire on interventional treatment of aorto-ostial lesions.</p><p><b>METHODS</b>A total of 86 consecutive patients underwent percutaneous coronary interventions (PCI) for aorto-ostial lesions were randomly divided into conventional treatment group (group A) and intra-aortic vacant guide wire group (group B). Standard PCI techniques were applied in group A and an intra-aortic vacant guide wire was placed outside the guiding catheter before the guiding catheter into the target coronary artery in group B on basis of standard PCI techniques. The number of guiding catheter, guide wire, X-ray exposure time, total PCI time, the incidence of pressure drop and malignant arrhythmia, contrast agent dose and the number of failure cases were compared between the two groups.</p><p><b>RESULTS</b>The number of used guide wire was similar between the groups (2.0 ± 1.1 vs. 2.2 ± 0.4, P > 0.05) and the number of guiding catheter used was significantly more in group A than in group B (2.3 ± 1.1 vs. 1.3 ± 0.5, P < 0.01). The X-ray exposure time (18.8 min ± 6.9 min vs. 14.2 min ± 5.7 min, P < 0.01) was significantly less in groups B and the total PCI time (31.2 min ± 8.1 min vs. 20.1 min ± 4.5 min, P < 0.01) and the amount of contrast agent (193.5 ml ± 25.4 ml vs. 130.6 ml ± 32.8 ml, P < 0.01) and the frequency of pressure drop (19 cases vs. 2 cases, P < 0.01) were all significantly higher in group A than in group B. Incidence of malignant ventricular arrhythmia (8 vs. 0) and procedure failure (6 vs. 0) was also higher in group A compared to group B.</p><p><b>CONCLUSION</b>The method of using Intra-aortic vacant guide wire is associated with reduced risk and improved success rate of PCI for aorto-ostial lesions.</p>