Effect of short-term high-dose atorvastatin on systemic inflammatory response and myocardial ischemic injury in patients with unstable angina pectoris undergoing percutaneous coronary intervention

Background Percutaneous coronary intervention （PCI） could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property.The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI.Methods From March 2012 to May 2014,one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital,were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group （HD group,n=56） or 20 mg/d as normal dose group （ND group,n=57） or an additional single high loading dose （80 mg） followed 6-day atorvastatin 20 mg/d as loading dose group （LD group,n=52）.Plasma C-reactive protein （CRP） and interleukin-6 （IL-6） levels were determined before intervention and at 5 minutes,24 hours,48 hours,72 hours,and 7 days after intervention.Creatine kinase-myocardial isoenzyme （CK-MB） and cardiac troponin I （cTnl） were measured at baseline and then 24 hours following PCI.Results Plasma CRP and IL-6 levels increased from baseline after PCI in all groups.CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI.Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group （（9.14±3.02） mg/L） than in the LD group （（11.06±3.06） mg/L） and ND group （（12.36±3.08） mg/L,P ＜0.01）; this effect persisted for 72 hours.IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group （（16.19±5.39） ng/L and （14.26±4.12） ng/L,respectively）） than in the LD group （（19.26±6.34） ng/L and （16.03±4.08） ng/L,respectively,both P ＜0.05） and ND group （（22.24±6.98） ng/L and （17.24±4.84） ng/L,respectively）.IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups.Although PCI cau     

CYP2C19基因多态性影响稳定型冠心病患者氯吡格雷治疗后血小板P2Y12受体信号通路的分子机制

 目的  探讨中国冠心病患者CYP2C19基因多态性影响氯吡格雷疗效的分子机制。方法  入组208例接受冠状动脉介入治疗(percutaneous coronary intervention, PCI)的稳定型冠心病(stable coronary artery disease, SCAD)患者,采用PCR产物直接测序的方法对所有纳入对象进行CYP2C19基因多态性分析,血栓弹力图检测300 mg氯吡格雷负荷量24 h后的血小板聚集率,流式细胞仪检测P2Y12受体下游信号分子血管扩张刺激磷蛋白血小板反应性指数(vasodilator-stimulated phosphorylation-platelet reactivity index, VASP-PRI)和Akt磷酸化(P-Akt)水平。结果  208例患者中85例(40.9%)的基因型为CYP2C19*1/*1 (非携带者),无等位基因缺失(loss-of-function, LOF),93例(44.7%)为CYP2C19*1/*2或CYP2C19*1/*3(1个LOF),30例(14.4%)为CYP2C19*2/*2或CYP2C19*2/*3 (2个LOF)。氯吡格雷治疗后的血小板聚集率及VASP-PRI随着携带LOF数目的增加而增加,而P-Akt只在2个LOF的情况下才会明显增加。VASP-PRI与氯吡格雷治疗后血小板聚集率有相关性(r=0.672,P<0.001),但是与P-Akt不相关。结论  携带2个CYP2C19 LOF的SCAD患者经氯吡格雷治疗后血小板聚集率更高,并与活性更高的G蛋白偶联受体P2Y12信号通路相关。     

Platelet function monitoring guided antiplatelet therapy in patients receiving high-risk coronary interventions

Background Large-scale clinical trials have shown that routine monitoring of the platelet function in patients after percutanous coronary intervention （PCI） is not necessary. However, it is still unclear whether patients received high-risk PCI would benefit from a therapy which is guided by a selective platelet function monitoring. This explanatory study sought to assess the benefit of a therapy guided by platelet function monitoring for these patients. Methods Acute coronary syndrome （ACS） patients （n=384） who received high-risk, complex PCI were randomized into two groups. PCI in the two types of lesions described below was defined as high-risk, complex PCI： lesions that could result in severe clinical outcomes if stent thrombosis occurred or lesions at high risk for stent thrombosis. The patients in the conventionally treated group received standard dual antiplatelet therapy. The patients in the platelet function monitoring guided group received an antiplated therapy guided by a modified thromboelastography （TEG） platelet mapping： If inhibition of platelet aggregation （IPA） induced by arachidonic acid （AA） was less than 50% the aspirin dosage was raised to 200 mg/d; if IPA induced by adenosine diphosphate （ADP） was less than 30% the clopidogrel dosage was raised to 150 mg/d, for three months. The primary efficacy endpoint was a composite of myocardial infarction, emergency target vessel revascularization （eTVR）, stent thrombosis, and death in six months. Results This study included 384 patients; 191 and 193 in the conventionally treated group and platelet function monitoring guided group, respectively. No significant differences were observed in the baseline clinical characteristics and interventional data between the two groups. In the platelet function monitoring guided group, the mean IPA induced by AA and ADP were （69.2＋24.5）% （range, 4.8% to 100.0%） and （51.4＋29.8）% （range, 0.2% to 100.0%）, respectively. The AA- induced IPA of forty-three （22.2%）     

吸烟与CYP2C19功能缺失性等位基因的交互作用对急性冠脉综合征患者氯吡格雷抗血小板反应性的影响

目的 探讨吸烟和CYP2C19功能缺失性等位基因交互作用对氯吡格雷抗血小板反应性的影响。方法 该研究连续募集2011年9月—2013年9月解放军总医院住院并接受阿司匹林和氯吡格雷双联抗血小板治疗的急性冠脉综合征（ACS）患者。采用光密度比浊法（LTA）测定氯吡格雷治疗前后的血小板聚集率,SnaPshot法检测CYP2C19功能缺失性等位基因变异型。利用单因素和多因素统计方法,分析吸烟和CYP2C19基因型交互作用对氯吡格雷治疗前后的血小板聚集率和治疗期间高血小板反应性（HPR）的影响。结果 该研究共纳入500例患者,吸烟组203例（40.6%）,非吸烟组297例（59.4%）。在非吸烟组,氯吡格雷治疗后的稳定血小板聚集率在CYP2C19＊2携带者（＊1/＊2：43.24±19.39;＊2/＊2：53.52±19.88）和非携带者（＊1/＊1：37.91±19.12）之间差异均有统计学意义（校对后P值分别为P=0.029,P〈0.001）;而在吸烟组中未见上述差异。非吸烟组中至少一个CYP2C19＊2等位基因携带者与非携带者之间的HPR的发生率差异有统计学意义（校正后OR：2.13,95%CI：1.23-3.72,P=0.008）,而在吸烟组中未见上述差异（校正后OR：1.41;95%CI：0.65-3.04,P=0.387）。结论 吸烟和CYP2C19功能缺失性等位基因的交互作用能够影响ACS患者中氯吡格雷的抗血小板反应性。     

经皮冠状动脉介入治疗的急性冠状动脉综合征患者CYP2C19基因多态性分布及新加丹参饮对CYP2C19基因缺陷患者的干预作用

目的 研究新加丹参饮对气滞血瘀型急性冠状动脉综合征经皮冠状动脉介入（acute coronary syndrome with percutaneous coronary intervention,ACS-PCI）患者的干预作用,并对CYP2C19基因缺陷患者进行亚组分析。方法 将92例气滞血瘀型ACS-PCI患者随机分为对照组和治疗组,对照组予常规西医治疗,治疗组在此基础上加用新加丹参饮进行治疗,2周后观察患者的肝肾功能、心肌酶谱、心绞痛疗效、中医临床症状及血小板聚集率等指标,来评价新加丹参饮的疗效。亚组研究：探讨CYP2C19基因多态性与氯吡格雷抵抗（clopidogrel resistance,CR）的相关性及新加丹参饮对CR患者的干预疗效。结果 治疗后治疗组心绞痛症状、中医症状改善情况明显优于对照组（P<0.05）;治疗组纤维蛋白原、血小板聚集率改善作用优于对照组（P<0.05）;CYP2C19*2基因型、CYP2C19*3基因型均与CR具有显著相关性（P<0.05）;CYP2C19*2突变纯合子合并CYP2C19*3突变杂合子发生CR概率（4/4）最高,随着突变链增多,CR发生率有一定上升趋势;治疗组在降低CR患者血清纤维蛋白原方面优于对照组（P<0.05）,在降低CR患者血小板聚集率方面与对照组相当（P>0.05）。结论 新加丹参饮干预治疗能有效改善患者心绞痛症状、中医临床症状;CYP2C19基因多态性与CR的发生密切相关;新加丹参饮对CR患者的纤维蛋白原、血小板聚集率具有改善作用。     

Pulmonary vein antrum isolation of pre-excited atrial fibrillation

Background Pulmonary vein antrum isolation (PVAI) of pre-excited atrial fibrillation (AF) is controversial. This study aimed to observe the therapeutic effects of PVAI on pre-excited AF.

Methods Twenty-nine patients with pre-excited AF were prospectively divided into a PVAI group (group I, 19 cases) and a control group (group II, 10 cases). To each case in group I, PVAI was performed, and then electroanatomical mapping of accessory pathways (AP) and ablation were constructed on a three-dimensional (3D) map of the valve annulus. Only AP ablation was performed in each case of group II.

Results Of the 29 cases, three were found to have dual APs, two had intermittent APs, and the remaining 24 had single APs. All APs were successfully ablated after the procedure. There were no significant statistical differences in the AP procedure duration ((77.4±21.3) minutes vs. (85.3±13.1) minutes), the AP ablation time ((204±34) seconds vs. (223±62) seconds) and the AP X-ray exposure time ((18.6±4.4) minutes vs. (19.1±4.5) minutes) respectively between groups I and II. As compared with the control group (5 of 10 cases, 50%), the PVAI group had a significantly lower AF recurrence rate (2 of 19 cases, 11%; P <0.05) during follow-up of (20.5±10.0) months. All seven patients who recurred were successfully abolished by a second ablation.

Conclusions In patients with pre-excited AF, PVAI is an effective therapeutic approach with a low AF recurrence rate. 3D electroanatomical maps of AP contributed to the high success rate of ablation without significantly prolonging of operational duration and X-ray exposure time.

     

血栓弹力图预测CYP2C19基因型对指导经皮冠状动脉介入术后氯吡格雷治疗的价值

目的研究血栓弹力图对细胞色素P450系统药物代谢酶CYP2C19基因型的预测作用及对经皮冠状动脉介入术(PCI)后氯吡格雷治疗的指导价值。方法选择2012年1月至2012年8月于我科行PCI治疗的冠心病患者70例,均给予阿司匹林和氯吡格雷双联抗血小板药物治疗。根据对二磷酸腺苷(ADP)诱导的血小板聚集抑制率的测定结果分为氯吡格雷抵抗组和氯吡格雷敏感组。检测70例患者CYP2C19的基因型;根据不同等位基因功能缺失,分为快代谢基因型(*1/*1)、中间代谢基因型(*1/*2,*1/*3)和慢代谢基因型(*2/*2,*2/*3,*3/*3)。比较氯吡格雷抵抗组和氯吡格雷敏感组患者的一般临床资料、生化指标和CYP2C19基因型的差异,多因素logistic回归分析氯吡格雷抵抗的危险因素。利用受试者工作曲线(ROC)检验血小板聚集抑制率预测CYP2C19基因型的效力。结果氯吡格雷抵抗组(31例)和氯吡格雷敏感组(39例)高密度脂蛋白水平、CYP2C19基因型的差异均有统计学意义(P<0.05)。逐步向前logistic回归分析结果显示CYP2C19慢代谢基因型和高密度脂蛋白水平降低为氯吡格雷抵抗的独立危险因素(P<0.05)。利用血小板聚集抑制率预测CYP2C19基因型的ROC曲线下面积(AUC)为0.847(95%CI:0.729～0.965,P=0.003),提示效力较好;当血小板聚集抑制率取最佳临界值(39.45%)时,诊断CYP2C19基因型为慢代谢型的敏感性为85.7%,特异性为77.8%,阳性预测值为30%,阴性预测值为98%。结论携带CPY2C19慢代谢基因型和高密度脂蛋白水平降低是导致氯吡格雷抵抗的独立危险因素。当血小板聚集抑制率小于39.45%时,应对患者做CYP2C19基因型的检测,以调整治疗方案。     

Efficacy of the long-acting octreotide formulation in patients with thyroid-stimulating hormone-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure

Background  Little information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. 

Methods  Fifteen patients with TSH-secreting pituitary adenomas (8 men and 7 women), who previously underwent incomplete surgical resection and/or adjuvant radiotherapy (n=12) and failure of octreotide treatment (n=15), followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables.

Results  After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine (FT4) ((16.02±1.72) pmol/L) and free triiodothyronine (FT3) ((2.87±0.43) pmol/L) levels of 15 patients significantly decreased compared with those after octreotide-treatment (FT4, (35.36±7.42) pmol/L, P <0.001; FT3, (17.85±7.22) pmol/L, P <0.001). Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment ((0.72±0.21) mU/L) and were significantly lower than the pretreatment value ((5.27±1.04) mU/L, P <0.001), post-surgery value ((3.37±0.31) mU/L, P <0.001) and post-octreotide-treatment value ((4.52±0.41) mU/L, P <0.001). In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis.

Conclusion  The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.

     

Jitter analysis with concentric needle electrodes in the extensor digitorum communis for the diagnosis of myasthenia gravis: a pilot study

Background Single-fiber electromyography is the most sensitive neurophysiological test for the diagnosis of myasthenia gravis （MG）,but its use is limited by the potential risk of transmission of infections.Jitter analysis with disposable concentric needle electrodes （CNEs） is therefore being investigated.This pilot study aimed to evaluate jitter analysis with CNEs for the diagnosis of MG.Methods Forty-two healthy Chinese volunteers and 44 MG patients were prospectively enrolled.MG patients were classified according to the Osserman classification,and acetylcholine receptor antibody titer was measured.Jitter analysis with CNEs in the extensor digitorum communis and repetitive nerve stimulation （RNS） testing were performed.Jitter was expressed as the mean consecutive difference （MCD）,and 20 action potential pairs were analyzed in each subject.The mean MCD in each subject and the mean individual MCD of all action potential pairs were compared between groups.Results The mean MCD and mean individual MCD were higher in MG patients （（42.3±20.0） μs and （42.2±26.0） μs） than in healthy volunteers （（23.0±3.1） μs and （22.8±7.5） μs）.The area under the receiver operating characteristic curve for the mean MCD of MG patients and healthy volunteers combined was 0.85.The mean MCD and mean individual MCDwere higher in generalized MG patients （（64.1±18.5） μs and （63.6±30.0） μs） than in ocular MG patients （（33.1±12.0） μs and （33.2±17.6） μs）,and were higher in MG patients with abnormal RNS results （（57.2±18.3） μs and （57.3±29.2） μs） than in MG patients with normal RNS results （（32.9±14.8） μs and （32.7±18.3） μs）.Abnormal RNS results were observed in 38.60% （17/44） of MG patients and abnormal jitter were observed in 72.70% （32/44） of MG patients.Conclusion Jitter analysis with CNEs is feasible for the diagnosis of MG.     

Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to hepatitis B virus-related cirrhosis

Background  The heme oxygenase/carbon monoxide (HO/CO) system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC.

Methods  According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group (group N) consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen (PaO₂) and oxygen saturation (SaO₂) were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome (HRS), upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis (SBP) in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades (I, II, III, and IV), PaO₂, SaO₂ and hypoxemia were analyzed.

Results  The COHb level in group P-H ((1.672±0.761)%) was significantly higher than that in group N ((0.983±0.231)%) (P <0.01), and the level in group H ((2.102±1.021)%) was significantly higher than groups P-H and N (P <0.01). A positive correlation was observed between the COHb concentration and the grade of HE (r_s=0.357, P=0.004). There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices ((2.302±1.072)% vs. (1.802±1.041)%, P >0.05) or the occurrence of SBP ((2.960±0.561)% vs. (2.030±1.021)%, P >0.05). Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS ((2.502±1.073)% vs. (1.981±1.020)%, P=0.029). The COHb level had a negative correlation with PaO₂ (r=−0.335, P=0.007) while no statistically significant relationship was found with SaO₂ (r=−0.071, P >0.05). However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased ((2.621±0.880)% vs. (1.910±0.931)%, P=0.011).

Conclusions  COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.

     

CYP2C19基因多态性对ACS患者PCI术后血小板聚集率的影响

目的 探讨急性冠状动脉综合征（ACS）患者CYP2C19基因多态性对经皮冠状动脉介入治疗（PCI）后服用氯吡格雷血小板抑制率的影响。方法 选择诊断为ACS且进行PCI术的537例患者为研究对象,分析用药后血小板抑制率与CYP2C19基因多态性的相关性。结果 与快代谢者（216例,40.22%）相比,中间代谢者（246例,45.81%）的血小板抑制率明显降低{（44.86±12.36）% vs. （55.77±15.23）%},差异具有统计学意义（t=8.384,P<0.001）;慢代谢者（75例,13.97%）的血小板抑制率与快代谢者{（36.75±12.77）% vs. （55.77±15.23）%}和中间代谢者{（36.75±12.77）% vs.（44.86±12.36）%}相比,均显著降低,差异具有统计学意义（?t=9.693,?P<0.001;?t=4.932,?P<0.001）。结论 CYP2C19基因多态性与ACS患者行PCI术后服用氯吡格雷的血小板抑制率存在相关性,CYP2C19基因多态性可作为PCI术患者抗血小板用药策略的参考依据。     

Short-term safety and efficacy of the biodegradable iron stent in mini-swine coronary arteries

Background To overcome the drawbacks of permanent years. The bioabsorbable polymer vascular scaffold （BVS） stents, biodegradable stents have been studied in recent was the first bioabsorbable stent to undergo clinical trials, demonstrating safety and feasibility in the ABSORB studies. Iron can potentially serve as the biomatedal for biodegradable stents. This study aimed to assess the short4erm safety and efficacy of a biodegradable iron stent in mini-swine coronary arteries. Methods Eight iron stents and eight cobalt chromium alloy （VISION） control stents were randomly implanted into the LAD and RCA of eight healthy mini-swine, respectively. Two stents of the same metal base were implanted into one animal. At 28 days the animals were sacrificed after coronary angiography, and histopathological examinations were performed. Results Histomorphometric measurements showed that mean neointimal thickness （（0.46±0.17） mm vs. （0.45±0.18） mm, P=0.878）, neointimal area （（2.55±0.91） mm2 vs. （3.04±1.15） mm2, P=0.360） and percentage of area stenosis （（44.50±11.40）% vs. （46.00±17.95）%, P=0.845） were not significantly different between the iron stents and VISION stents. There was no inflammation, thrombosis or necrosis in either group. The scanning electron microscopy （SEM） intimal injury scores （0.75±1.04 vs. 0.88±0.99, P=0.809） and number of proliferating cell nuclear antigen （PCNA） positive staining cells were not significantly different between the two groups. The percentage of neointimal coverage by SEM examination was numerically higher in iron stents than in VISION stents （（84.38±14.50）% vs. （65.00±22.04）%, P=0.057）, but the difference was not statistically significant. Iron staining in the tissue surrounding the iron stents at 28 days was positive and the vascular wall adjacent to the iron stent had a brownish tinge, consistent with iron degradation. No abnormal histopathological changes were detected in coronary arteries or major organs. Conclusions The biodegradable iron stent has good biocompatibility and short-term safety and efficacy in the mini- swine coronary artery. Corrosion of iron stents is observed at four weeks and no signs of organ toxicity related to iron degradation were noted.     

Hydrogen sulfide defends against the cardiovascular risk of Nw-nitro-L-argininemethyl ester-induced hypertension in rats via the nitric oxide/endothelial nitric oxide synthase pathway

Background Dyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications.Previous studies have shown that hydrogen sulfide （H2S） protects against multiple cardiovascular disease states in a similar manner as nitric oxide （NO）,and NO/endothelial nitric oxide synthase （eNOS） pathway is the key route of NO production.The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw-nitro-L-argininemethyl ester （L-NAME）-induced hypertensive rats by NO/eNOS pathway.Methods Thirty-six 4-week old Sprague-Dawley （SD） male rats were randomly assigned to 6 groups （n=6）：control group,L-NAME group,control ＋ glibenclamide group,control ＋ NaHS group,L-NAME ＋ NaHS group,and L-NAME ＋ NaHS ＋ glibenclamide group.Measurements were made of plasma triglycerides （TG）,low-density lipoprotein （LDL）,high-density lipoprotein （HDL）,total cholesterol （CHO）,glutamic-pyruvic transaminase （ALT） levels after 5 weeks.Then measurements of NO level and proteins expression of eNOS,P-eNOS,AKT,P-AKT were made in liver tissue.Results After 5 weeks of L-NAME treatment,the blood pressure,plasma TG （（1.22±0.12） mmol/L in L-NAME group vs.（0.68±0.09） mmol/L in control group; P ＜0.05） and LDL （（0.54±0.04） mmol/L in L-NAME group vs.（0.28±0.02） mmol/L in control group; P ＜0.05） concentration were significantly increased,and the plasma HDL （（0.26±0.02） mmol/L in L-NAME group vs.（0.69±0.07） mmol/L in control group; P ＜0.05） concentration significantly decreased.Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS,diminished NO levels （（1.36±0.09） mmol/g protein in L-NAME group vs.（2.34±0.06） mmol/g protein in control group; P ＜0.05） and pathological changes of the liver.H2S therapy can markedly decrease the blood pressure （（37.25±4.46） mmHg at the fifth week; P ＜0.05）,and ameliorate the plasma TG （（0.59±0.06） mmHg）,     

Cigarette smoking contributes to idiopathic pulmonary fibrosis associated with emphysema

Background Combined emphysema and pulmonary fibrosis,including idiopathic pulmonary fibrosis （IPF）,is a distinct disorder described with upper-lobe emphysema and lower-lobe fibrosis on chest computed tomography.Smoking appears to be the predominant risk factor for this disorder.We aimed to compare clinical features,smoking history,physiological and radiological findings between IPF with and without emphysema.Methods A sample of 125 IPF patients over a period of 48 months were evaluated.High resolution CT scans were reviewed blinded to clinical data.The IPF patients with or without emphysema were classified accordingly.Results The prevalence of emphysema in this IPF sample was 70/125.IPF with emphysema was significantly associated with smoking status （OR 63; 95％ CI 4.4 to 915; P=0.002） and smoking pack year （OR 1.1; 95％ CI 1.05 to 1.13; P=-0.000）.The patients with IPF and emphysema had a higher decrease in carbon monoxide diffusing capacity adjusted for alveolar volume （（58±19）％ pred vs.（66：±：21）％ pred; P=-0.021） and a higher prevalence of pulmonary hypertension （24/70 vs.7/55; P=0.006）.The two groups of patients had similar forced and residual volumes.No significant differences were found in cell differentials of bronchoalveolar lavage or the scores of fibrosis on chest CT.Survival of the patients with emphysema was significantly less than that of patients with IPF alone.Conclusions Cigarette smoking induces IPF combined with emphysema.Emphysema further impairs physiological function and increases the prevalence of pulmonary hypertension that leads to poor prognosis.The inclusion of the patients with combined pulmonary fibrosis and emphysema in IPF clinical trials may lead to under evaluation of the effect of treatment in patients.     

Thiopurine methyltransferase gene polymorphisms and activity in Chinese patients with inflammatory bowel disease treated with azathioprine

Background  The thiopurine drugs are well established in the treatment of inflammatory bowel disease (IBD). However, uncertainty regarding the risk for neutropenia and hepatotoxicity deters its using. Thiopurine methyltransferase (TPMT) is the key enzyme in the metabolism of thiopurine. The aim of this study was to investigate the association of TPMT polymorphisms and activity with azathioprine (AZA)-related adverse events and clinical efficacy in Chinese Han patients with IBD.

Methods  Fifty-two Han IBD patients treated with AZA were assessed for TPMT*2, *3A, *3B, and *3C, and for adverse events. Then, using reverse-phase high-performance liquid chromatography, TPMT activity was measured in 13 patients to analyze its correlation with AZA-related toxicity and clinical efficacy.

Results  Of the 52 patients, five experienced myelotoxicity and one experienced hepatotoxicity during treatment. No TPMT*2, *3A, *3B or *3C polymorphisms were detected in any of the 52 patients. In the 13 patients with TPMT activity measurement, TPMT activity ranged from 7.2 to 28.8 U/ml packed red blood cells (pRBCs). Among the 5 patients who suffered from myelotoxicity, 3 were affected in the early stage of AZA therapy. In these 3 patients, TPMT levels were significantly lower than those in patients without myelotoxicity, which reached statistical significance ((9.3±2.1) U/ml pRBC vs. (18.0±6.2) U/ml pRBC; P=0.046). One patient who had higher TPMT activity (28.8 U/ml pRBC) suffered from hepatotoxicity during AZA therapy. Patients who achieved a clinical response had lower TPMT activity than those failed to respond ((13.7±3.5) U/ml pRBC vs. (22.0±5.5) U/ml pRBC; P=0.009).

Conclusions  TPMT variants do not completely account for the AZA-related myelotoxicity in Chinese Han IBD patients. However, measurement of TPMT activity may be helpful in reducing the risk of toxicity, and predicting the therapeutic efficacy.

     

CYP2C19基因多态性与氯吡格雷抗血小板作用的关系研究

目的探讨CYP2C19基因多态性与氯吡格雷抗血小板作用的关系。方法收集2017年12月25日～2018年10月9日我院治疗的250例冠心病患者,通过基因芯片检测试剂盒鉴定CYP2C19基因型,根据CYP2C19基因多态性检测结果将患者分为野生型组和突变型组。通过光比浊法测定两组患者的血小板抑制率,并比较两组患者的氯吡格雷抵抗情况。结果 250例患者中,CYP2C19野生型145例(58.00%),突变型105例(42.00%)。野生型组的血小板抑制率(75.96±11.50)%显著高于突变型组(47.13±7.97)%(P0.05)。250例患者中共有59例(23.6%)发生氯吡格雷抵抗现象,其中野生型组13例(8.97%),突变型组46例(43.81%),差异具有统计学意义(P0.05)。结论 CYP2C19基因多态性、糖尿病、体质指数是氯吡格雷抵抗的重要影响因素,检测CYP2C19基因多态性、是否患有糖尿病、体质指数有助于指导患者的抗血小板治疗。     

Proficiency of virtual reality simulator training in flexible retrograde ureteroscopy renal stone management

Background Minimally invasive flexible ureteroscopy techniques have widely adopted in the management of patients with renal stones. We performed this study to investigate the value of virtual reality simulator training in retrograde flexible ureteroscopy renal stone treatment for catechumen.     

冠心病血瘀证患者细胞色素P450 2C19＊17基因型分布与氯吡格雷治疗后血小板聚集率及出血风险的关系

目的：探讨细胞色素P450（cytochrome, CYP）2C19＊17等位基因变异对中国冠心病血瘀证患者经皮冠状动脉介入术（percutaneous coronary intervention, PCI）后应用氯吡格雷治疗的血小板聚集率及出血事件的影响。 方法：以限制性片段长度多态性聚合酶链反应基因分析方法检测CYP2C19＊17基因多态性,研究2009年7月至2011年4月福建省立医院心内科择期进行PCI成功的冠心病血瘀证患者520例。PCI术前常规服用阿司匹林300 mg、氯吡格雷300 mg。术前采血,制备富血小板血浆、贫血小板血浆及二磷酸腺苷（adenosine diphosphate, ADP）诱导剂,采用比浊法,以最终浓度为5 μmol/L ADP为诱导剂,在氯吡格雷治疗前及治疗后10 d,检测血小板聚集率。分析最大血小板聚集率（maximal aggregation, Aggmax）和残余血小板聚集率（5-min aggregation, Agglate）。 结果：试验发现有5.96%的患者发生心肌梗死血栓溶解术出血事件,而本试验中病人的CYP2C19＊17等位基因频率为7.98%。对于CYP2C19＊17等位基因携带者,其出血事件发生率远高于野生型（P＜0.01）;在基线水平,5 μmol/L ADP诱导的Aggmax和Agglate以及血小板聚集率在CYP2C19＊17各基因型之间并没有显著区别;然而经氯吡格雷治疗10 d后,CYP2C19＊17等位基因携带者与野生型相比,上述3项指标均明显降低（P＜0.01或P＜0.05）,血小板聚集抑制率显著高于野生型患者（P＜0.01）;携带有CYP2C19＊17等位基因的患者与野生型相比,具有更高的出血风险（P＜0.01）。 结论：冠心病血瘀证患者CYP2C19＊17等位基因携带者有着显著的氯吡格雷反应性且其出血风险明显增加。     

Impact of primary percutaneous coronary intervention on blood perfusion in nonculprit artery in patients with anterior ST elevation myocardial infarction

Background Recent studies have demonstrated that epicardial flow in nonculprit arteries,which has been assumed to be normal,was slowed in the setting of ST-elevation myocardial infarction (STEMI).Howev...