Comparison of the Efficacy of Drug-eluting Stents Versus Bare-metal Stents for the Treatment of Left Main Coronary Artery Disease

Background:

Recent studies reported that percutaneous coronary intervention with stent implantation was safe and feasible for the treatment of left main coronary artery (LMCA) disease in select patients. However, it is unclear whether drug-eluting stents (DESs) have better outcomes in patients with LMCA disease compared with bare-metal stent (BMS) during long-term follow-up in Chinese populations.

Methods:

From a perspective multicenter registry, 1136 consecutive patients, who underwent BMS or DES implantation for unprotected LMCA stenosis, were divided into two groups: 1007 underwent DES implantation, and 129 underwent BMS implantation. The primary outcome was the rate of major adverse cardiac events (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), and target lesion revascularization (TLR) at 5 years postimplantation.

Results:

Patients in the DES group were older and more likely to have hyperlipidemia and bifurcation lesions. They had smaller vessels and longer lesions than patients in the BMS group. In the adjusted cohort of patients, the DES group had significantly lower 5 years rates of MACE (19.4% vs. 31.8%, P = 0.022), CV death (7.0% vs. 14.7%, P = 0.045), and MI (5.4% vs. 12.4%, P = 0.049) than the BMS group. There were no significant differences in the rate of TLR (10.9% vs. 17.8%, P = 0.110) and stent thrombosis (4.7% vs. 3.9%, P = 0.758). The rates of MACE (80.6% vs. 68.2%, P = 0.023), CV death (93.0% vs. 85.3%, P = 0.045), TLR (84.5% vs. 72.1%, P = 0.014), and MI (89.9% vs. 80.6%, P = 0.029) free survival were significantly higher in the DES group than in the BMS group. When the propensity score was included as a covariate in the Cox model, the adjusted hazard ratios for the risk of CV death and MI were 0.41 (95% confidence interval [CI]: 0.21–0.63, P = 0.029) and 0.29 (95% CI: 0.08–0.92, P = 0.037), respectively.

Conclusions:

DES implantation was associated with more favorable clinical outcomes than BMS implantation for the treatment of LMCA disease even though there was no significant difference in the rate of TLR between the two groups.     

Short-term Rosuvastatin Treatment for the Prevention of Contrast-induced Acute Kidney Injury in Patients Receiving Moderate or High Volumes of Contrast Media: A Sub-analysis of the TRACK-D Study

Background:

Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown.

Methods:

In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200–300 ml, n = 712) or (high contrast volume [HCV], ≥300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days.

Results:

Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273).

Conclusions:

Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.     

Doxycycline attenuates acute lung injury following cardiopulmonary bypass: involvement of matrix metalloproteinases

Acute lung injury (ALI) was one of the major complications after cardiopulmonary bypass (CPB). Matrix metalloproteinases (MMPs) play an important role in ALI following CPB. In this study, we investigated the effects of doxycycline (DOX), a potent MMP inhibitor, on MMP-9 and ALI in the rat model of CPB. 48 adult male Sprague-Dawley rats were randomized into four groups: group I (Control group, underwent cannulation + heparinization only); group II (CPB group, underwent 60-minutes of normothermic CPB); group III (Low-dose treatment group, underwent 60-minutes of normothermic CPB with DOX gavage 30 mg/kg ×1 week ahead of CPB); and group IV (High-dose treatment group, underwent 60-minutes of normothermic CPB with DOX gavage 60 mg/kg ×1 week ahead of CPB). The effects of doxycycline on ALI were determined by measuring the lung Wet/Dry ratio, the inflammation of bronchoalveolar lavage fluid (BALF) and the ultrastructural changes of the lungs. The role of doxycycline on MMP-9 was assessed by the plasma concentration, the activity and the expression in lung tissue. Our results demonstrated that the lung Wet/Dry weight ratio and the inflammatory mediators (TNF-α, IL-1β) in BALF were decreased significantly with doxycycline treatment. The lung damages were attenuated by doxycycline. The levels of plasma concentration, the activity and the expression of MMP-9 in lung tissue were suppressed with doxycycline and the effects were dose dependent. Doxycycline could suppress the expression of MMP-9 and cytokines, and improve the ALI following CPB.     

中华眼镜蛇毒诱导HL-60细胞凋亡及其机制探讨

目的　观察中华眼镜蛇毒体外对白血病细胞凋亡的影响 ,并探讨其可能的作用机制。方法　本研究采用血清药理学方法 ,以人白血病细胞HL 60细胞为靶细胞 ,通过流式细胞仪分析、DNA片段凝胶电泳、免疫组织化学 (S P法 )观察中华眼镜蛇毒兔血清体外对细胞凋亡的诱导作用及癌基因表达的影响。结果　经DNA电泳、流式细胞仪分析显示 :中华眼镜蛇毒兔血清与HL 60细胞共同培养 48h可诱导其细胞凋亡增加 ,bcl 2、c myc基因蛋白表达下调。结论　中华眼镜蛇毒兔血清体外抑制HL 60细胞增殖可能与其诱导细胞凋亡及使细胞bcl 2、c myc基因蛋白表达下调密切相关     

Purification, characterization and biological activities of the l-amino acid oxidase from Bungarus fasciatus snake venom

l-Amino acid oxidases (LAAOs) are widely distributed in snake venoms, which contribute to the toxicity of venoms. However, LAAO from Bungarus fasciatus (B. fasciatus) snake venom has not been isolated previously. In the present study, LAAO from B. fasciatus snake venom was purified by SP-Sepharose HP anion exchange chromatography followed by Heparin-Sepharose FF affinity chromatography procedure and the purified enzyme was named BF-LAAO. BF-LAAO presented an estimated molecular weight of 55 kDa in SDS-PAGE and an apparent molecular weight of 70 kDa in size-exclusion chromatography suggesting that BF-LAAO is a monomeric protein. Kinetics studies showed that BF-LAAO was very active against l-Tyr, l-Asp, l-Phe, l-Glu, l-Trp, l-His, l-Gln, l-Ile, l-Met, l-Leu and moderately active against l-Lys, l-Arg, l-Ala and l-Asn. BF-LAAO exhibited a cytotoxic effect on A549 cells and caused up to 41.2% apoptosis of A549 cells following 12 h incubation period. In the mouse peritoneum, BF-LAAO provoked a marked increase in the number of neutrophils, lymphocytes and macrophages following injection. It also induced rabbit platelet aggregation in a dose-dependent manner. At 3 h following injection, BF-LAAO elicited severe inflammation in the gastrocnemius muscles of mice, but failed to induce significant organ damage. In conclusion, the cytotoxic and proinflammatory activities of BF-LAAO could be the main cause of the local inflammation, which helps us to understand the pathogenesis of snakebite.     

Immunoglobulin E (IgE) Responses to Paramyosin Predict Resistance to Reinfection with Schistosoma japonicum and Are Attenuated by IgG4

Schistosomiasis remains a public health concern in developing countries, and rapid reinfection fostered by continued exposure to contaminated water sources necessitates a vaccine to augment current mass treatment-based control strategies. We report isotype-specific (immunoglobulin A [IgA], IgE, IgG1, IgG4, and IgG) antibody responses to soluble worm antigen preparation and the recombinant vaccine candidates rSj97, rSj67, and rSj22 from a Schistosoma japonicum-infected cohort in Leyte, the Philippines, where schistosomiasis is endemic. Sera were collected from infected individuals 1 month posttreatment with praziquantel, and antibody responses were measured using a bead-based multiplex platform. Reinfection was monitored by stool sampling every 3 months, and data up to 1 year were included in the analysis (n = 553). In repeated-measures models, individuals with detectible IgE responses to rSj97 had a 26% lower intensity of reinfection at 12 months posttreatment compared to nonresponders after adjusting for age, gender, village, exposure, pretreatment infection intensity, and clustering by household (P = 0.018). In contrast, IgG4 responses to rSj97 as well as rSj67 and rSj22 were associated with markedly increased reinfection intensity. When stratified by IgG4 and IgE responder status, individuals with IgE but not IgG4 responses to rSj97 (n = 16) had a 77% lower intensity of reinfection at 12 months compared to individuals with IgG4 responses but not IgE responses (n = 274), even after adjusting for potential confounders (P = 0.016). Together with our previously described protective cytokine responses, these data further support paramyosin as a leading vaccine candidate for human schistosomiasis japonica and underscore the importance of careful adjuvant selection to avoid the generation of blocking IgG4 antibody responses.Schistosomiasis, caused by parasitic helminths of the genus Schistosoma, remains a major public health concern and currently infects 200 million individuals with 600 million individuals at risk of infection in 74 developing countries (19). National control strategies focusing on mass chemotherapy with praziquantel have significantly reduced severe liver and urinary tract pathology; however, rapid reinfection with consequent subtle morbidities such as anemia, malnutrition, and cognitive impairment persist despite years of annual treatment (30). Continued exposure to contaminated water sources mandates alternative control strategies such as vaccine-linked chemotherapy (3).In vitro studies have demonstrated that schistosome larvae are susceptible to damage in the presence of sera from infected individuals together with leukocytes from uninfected donors, suggesting that parasite-specific antibody-dependent cellular cytotoxicity (ADCC) plays a key role in parasite elimination (8). Subsequent investigations identified the role of protective immunoglobulin E (IgE), IgA, and IgG antibody isotypes (11, 23, 29) and the participation of eosinophils and mast cells in orchestrating this attack (7, 12). However, several studies have also demonstrated the presence of inhibitory antibodies which block schistosomular killing (22, 28). In particular, the antibody isotype IgG4 is a poor initiator of ADCC and blocks killing by competing with protective isotypes (29). These data suggest that schistosomes induce both protective and antagonistic antibody responses, which may alter the balance between parasite elimination and immune evasion (3).Consonant with in vitro studies, several immunoepidemiologic surveys conducted in areas where schistosomiasis is endemic have demonstrated associations between antibody responses to crude parasite antigens and reinfection outcomes in humans. Protective IgE responses to worm (17, 24) and egg (43) antigens have been described across schistosome species, as well as IgA responses mediating antifecundity effects (23). These cohort studies have also described antiparasite IgG4 (16, 24, 32), IgM, and IgG2 (5, 22, 28) as isotypes associated with susceptibility.Based on a model of antibody-mediated protection, the antigenic targets of both protective antibody isotypes and protective monoclonal antibodies have been identified in parasite extracts and genomic libraries. Numerous candidates have been identified (4), and a panel of the most promising of these was evaluated in immunoepidemiologic studies in Egypt (2), Brazil (35), and to a limited extent in China and the Philippines (1, 32). Despite this progress (3), only one vaccine candidate (Schistosoma haematobium glutathione S-transferase) has advanced to early-phase clinical trials (10).We have previously described cytokine responses to crude antigen preparations (soluble worm antigen preparation [SWAP], SEA) and defined vaccine candidates (Sj97, Sj67, and Sj22) in a cohort of schistosomiasis-infected individuals between 7 and 30 years old and residing in Leyte, the Philippines (31). Here, we extend this work by measuring isotype-specific (IgA, IgE, IgG1, IgG4, and total IgG, henceforth referred to as IgG) antibody responses to these antigens in the same cohort and evaluating their association with resistance to reinfection over 12 months of posttreatment follow-up. We report that IgE responses to rSj97 are associated with resistance to reinfection and are attenuated by IgG4.     

Analysis of risk and protective factors associated with retinal nerve fiber layer defect in a Chinese adult population

AIM: To investigate the risk and protective factors associated with the retinal nerve fiber layer defect (RNFLD) in a Chinese adult population. METHODS: This study was a cross-sectional population-based investigation including employees and retirees of a coal mining company in Kailuan City, Hebei Province. All the study participants underwent a comprehensive systemic and ophthalmic examination. RNFLD was diagnosed on fundus photographs. Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD. RESULTS: The community-based study included 14 440 participants. There were 10 473 participants in our study, including 7120 males (68.0%) and 3353 females (32.0%). The age range was 45-108y, averaging 59.56±8.66y. Totally 568 participants had RNFLD and the prevalence rate was 5.42%. A higher prevalence of RNFLD was associated with older age [P<0.001, odds ratio (OR): 1.032; 95% confidence interval (CI): 1.018-1.046], longer axial length (P=0.010, OR: 1.190; 95%CI: 1.042-1.359), hypertension (P=0.007, OR: 0.639; 95%CI: 0.460-0.887), and diabetes mellitus (P=0.019, OR: 0.684; 95%CI: 0.499-0.939). The protective factors of RNFLD were visual acuity (P=0.038, OR: 0.617; 95%CI: 0.391-0.975), and central anterior chamber depth (P=0.046, OR: 0.595; 95%CI: 0.358-0.990). CONCLUSION: In our cross-sectional community-based study, with an age range of 45-108y, RNFLD is associated with older age, longer axial length, hypertension, and diabetes mellitus. The protective factors of RNFLD are visual acuity and central anterior chamber depth. These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.     

日本血吸虫副肌球蛋白合成肽的免疫学鉴定

目的 鉴定日本血吸虫副肌球蛋白合成肽Sj97-P22。 方法 27只雌性C57BL/6小鼠随机均分为合成肽Sj97-P22免疫组、无关肽免疫组和PBS免疫组,分别于尾基部皮下注射与完全福氏佐剂等体积充分混匀的合成肽Sj97-P22（100 μg）乳化物、无关肽（100 μg）乳化物和PBS乳化物,抗原免疫剂量为100 μg/（只·次）,共免疫2次,间隔1周。于免疫后7~10 d分离各组小鼠脾单个核细胞,运用流式细胞技术三色标记法检测其CD4^＋ T细胞胞内因子干扰素γ（IFN-γ）和白介素4（IL-4）。将Sj97-P22免疫小鼠或PBS免疫小鼠的脾单个核细胞分别与Sj97-P22、无关肽或PBS共培养,采用3H-TdR掺入法观察细胞增殖效果,并用ELISA法检测细胞培养上清中IL-2、IFN-γ和IL-4的浓度。 结果 Sj97-P22免疫组小鼠脾脏CD4⁺ T细胞中胞内分泌IFN-γ的细胞百分率为（8.05±0.54）%,显著高于无关肽免疫组[（4.74±1.04）%]和PBS免疫组[（6.51±0.49）%] （P＜0.05）;而分泌IL-4的细胞百分率[（0.60±0.11）%]显著低于PBS免疫组[（1.31±0.27）%]（P＜0.05）,与无关肽免疫组[（0.84±0.08）%]间的差异则无统计学意义（P＞0.05）。Sj97-P22可明显刺激Sj97-P22免疫小鼠脾单个核细胞增殖,增殖指数达到3.12±1.59,细胞培养上清中IL-2和IFN-γ浓度分别为（9.13±1.54）和（39.75±9.69）pg/ml,与无关肽和PBS刺激相比显著升高（P＜0.05）,而IL-4浓度在3个刺激物间的差异无统计学意义（P＞0.05）。Sj97-P22不能刺激PBS免疫鼠脾单个核细胞增殖及培养上清中IL-2、IFN-γ及IL-4浓度变化。 结论 Sj97-P22可能是C57BL/6小鼠特异的Th1型表位。     

口腔扁平苔癣固有层TNF-α、TGF-β的表达及其临床意义

目的：观察肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β1、TGF-β2）在口腔扁平苔癣（OLP）固有层中的表达特征及其意义。 方法： 用免疫组织化学方法检测TNF-α、TGF-β1，TGF-β2在OLP和正常口腔粘膜（NOM）组织中的细胞定位和表达量。 结果： OLP固有层中TNF-α阳性率77.27%(17/22), 表达权重与对照组相比P<0.01。阳性信号主要位于巨噬细胞、淋巴细胞等胞浆内或胞膜上。TGF-β1阳性率45.45%, 表达权重与对照组相比P<0.05, 主要分布于巨噬细胞、内皮细胞和成纤维细胞内。TGF-β2阳性率27.27(6/22), 表达权重与对照组相比P>0.05，可见于细胞外间质、成纤维细胞等。 结论： OLP固有层中，TNF-α和TGF-β1的表达及其细胞定位对局部炎症的发展和维持起着重要作用。     

抗VEGF药物治疗特发性CNV的效果及对眼压、BCVA、mfERG的影响

目的：探讨抗血管内皮生长因子(VEGF)药物治疗脉络膜新生血管(CNV)的疗效及对眼压、最佳矫正视力(BCVA)及多焦视网膜电图(mfERG)的影响。

方法：选取2015-02/2017-01在我院治疗的特发性CNV患者44例44眼,均给予玻璃体腔注射抗VEGF药物治疗,观察患者治疗前后BCVA、眼压、mfERG及中央视网膜厚度(CRT)的变化情况。

结果：治疗后1、3mo BCVA和CRT均较治疗前明显改善(P<0.05),其中治疗后3mo BCVA和CRT分别为0.60±0.15和278.43±40.10μm,明显较治疗后1mo改善(P<0.05)。治疗后1、3mo和治疗前眼压比较无明显变化(P>0.05)。治疗后1、3mo Ring1、Ring2和Ring4 NI-P1振幅密度均较治疗前提高(P<0.05); 治疗后3mo,Ring3 NI-P1振幅密度均较治疗前和治疗后1mo提高(P<0.05); 治疗后1mo,Ring5 NI-P1振幅密度较治疗前和治疗后3mo均提高(P<0.05); 治疗后1、3mo和治疗前Ring6 NI-P1振幅密度比较无明显变化(P>0.05)。

结论：抗VEGF药物治疗特发性CNV有较好的效果,能改善患者视力及黄斑区视网膜功能,降低视网膜厚度,且不影响眼压。