[Clinical application value of modified Lee grading system to evaluate the degree of foraminal stenosis in patients with intervertebral foraminal lumbar disc herniation].

Objective: To investigate the clinical application value of the modified Lee grading system (abbreviated as the modified system) in evaluating the degree of intervertebral foraminal stenosis(IFS) in patients with foraminal lumbar disc herniations(FLDH). Methods: MRI data of 83 patients with FLDH-IFS (34 patients in the operation group and 49 patients in the conservative group) in Yantai Affiliated Hospital of Binzhou Medical University and Yantai Yantaishan Hospital from March 2018 to February 2021 were retrospectively collected. There were 43 males and 40 females, ranged from 34 to 82 years old, with an average of (61±10) years. MRI images of selected patients were independently evaluated and recorded by two radiologists in a blind method, using both the Lee grading system (abbreviated as Lee system) and the modified system, respectively and each method was evaluated twice. The difference between the evaluation level of the two systems, and the agreement of observer assessments of the two systems were compared, and the correlation between the evaluation level of the two grading systems and the clinical treatment modalities was analyzed. Results: The percentage of nongrade 3 (grade 0-2) patients with effective conservative treatment according to the two grading systems was 94.6 % (139/147) and 64.2 % (170/265), respectively. The percentage of grade 3 patients requiring surgical treatment according to the two grading systems was 69.2 % (128/185) and 61.2 % (41/67), respectively. There was a statistically significant difference between the evaluation levels of the modified system and the Lee system (Z=-5.16, P=0.001). In the Lee system, the intra-observer observation consistency Kappa values of the two radiologists were 0.735 and 0.542, respectively, which were highly and moderately consistent; and the inter-observer observation consistency Kappa values were 0.426-0.521, which were moderate consistency. In the modified system, the intra-observer consistency Kappa values of the two radiologists were 0.900 and 0.921, respectively, and the consistency was almost completely consistent; and the inter-observer consistency Kappa values were 0.783-0.861, which were highly consistent or almost completely consistent. Lee system and clinical treatment modalities was correlative (rs=0.39,P<0.001), and modified system and clinical treatment modalities was correlative (rs=0.61,P<0.001). Conclusion: According to FLDH-IFS, the modified system can comprehensively and accurately grade, with high reliability and reproducibility. The evaluation level has a more significant correlation with clinical treatment modalities.

Acute heat stress alters the expression of genes and proteins associated with the unfolded protein response pathway in the liver of broilers.

1. The aim of this study was to explore the effects of acute heat stress on serum hormone levels and the expression of genes and proteins related to the unfolded protein response (UPR) pathway and apoptotic process in the liver of broilers.2. A total of 144 Arbor Acres broilers (35-d-old) were randomly allocated to 4 different environmental-controlled chambers for acute heat exposure. The temperature of the 4 environmental chambers was adjusted to 26°C (control), 29°C, 32°C, and 35°C within 1 h, respectively. The blood and liver samples were collected after 6 h of constant heat exposure at set temperatures.3. The results showed that 6 h of acute heat stress increased serum hormone levels and up-regulated the expression of heat shock protein. The endoplasmic reticulum (ER) stress markers, GRP78 and GRP94, in the liver of broilers were significantly upregulated at the mRNA and protein levels. The PERK, IRE1, and XBP1 genes, which are involved in the unfolded protein response signalling, were significantly up-regulated at the mRNA levels. However, other pro-apoptotic genes showed no significant changes in the liver of broiler chickens in all groups except for upregulation of the anti-apoptotic gene BCL-xl.4. The results suggested that broilers have tolerance to acute heat stress to a certain extent. The UPR activation can alleviate ER stress and further prevent apoptosis in the liver of broilers under short-term exposure to high ambient temperatures.

[A multicenter randomized controlled study of bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang in the treatment of patients newly diagnosed with Helicobacter pylori infection and dyspepsia].

Objective: To investigate the Helicobacter pylori (H. pylori) eradication rate and improvement of dyspepsia in patients who were newly diagnosed with H. pylori infection and dyspepsia and treated by bismuth-containing quadruple therapy followed by Jing-Hua-Wei-Kang(JHWK). Methods: Patients who were newly diagnosed with dyspepsia and H. pylori infection and treated in 16 medical centers in China between December 1, 2017 and September 30, 2019 were randomly divided into two groups. The experimental group received bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days), followed by JHWK (30 days), and the course of treatment was 44 days in total. In the control group, the administration regimen was bismuth-containing quadruple therapy (esomeprazole+amoxicillin+furazolidone+colloidal bismuth pectin capsule, 14 days). The main outcome measure was H. pylori eradication rate, while the secondary outcome measures were dyspepsia symptom changes and adverse events during the treatment and the 1st month after treatment. Results: A total of 1 054 patients were included in the study. There were 522 cases enrolled in the experimental group, including 224(42.91%) men and 298(57.09%) women, and the age was 53(26, 73) years old; 532 cases enrolled in the control group, including 221(41.54%) men and 311(58.46%) women, and the age was 46(22, 71) years old. Based on PP analysis, it was found that the H. pylori eradication rate in the experimental group was significantly higher than those in the control group (93.85% vs 87.88%, P=0.001). In the group of all enrolled patients, the symptom dyspepsia after H. pylori eradication was significantly improved compared with that before treatment [4(4, 7) vs 15(10, 22), P<0.001], so was the superior and middle abdominal pain [1(1, 4) vs 4(1, 8), P<0.001], the postprandial fullness [1(1, 4) vs 4(4, 9), P<0.001], the early satiety [1(1, 1) vs 4(1, 4), P<0.001], and the heartburn [1(1, 1) vs 1(1, 4), P<0.001]. The symptom dyspepsia after treatment was significantly improved compared with that before treatment in the experimental, the control groups, the successful and the unsuccessful H. pylori eradication groups. The superior and middle abdominal pain after treatment was signifcantly improved than that before treatment [1(1, 2) vs 1(1, 4), P<0.001], so were the postprandial fullness [1(1, 3) vs 1(1, 4), P=0.002] and the dyspepsia[4(4, 7) VS 7(4, 10), P<0.001]. There was no statistically significant difference in the incidence of adverse events between the experimental group and the control group (1.34% vs 0.38%, P=0.09). Conclusions: Compared with bismuth-containing quadruple therapy, bismuth-containing quadruple therapy followed by JHWK significantly improves the H. pylori eradication rate without increasing the incidence of adverse events. H. pylori eradication therapy can improve symptoms of patients with H. pylori infection and dyspepsia.

[Clinical and immunological characteristics of myositis complicated with thromboembolism].

OBJECTIVE: To investigate and analyse the clinical and immunological features of patients with myositis complicated with thromboembolism. METHODS: We identified a cohort of 390 myositis patients diagnosed with myositis admitted to People's Hospital of Peking University from 2003 to 2019. The patients were retrospectively enrolled in this investigation. According to the outcome of the color Doppler ultrasound, CT pulmonary angiography, pulmonary ventilation and perfusion scan patients were divided into myositis with and without thromboembolism group. Demographic, clinical (heliotrope rash, Gottron's sign/papules, periungual erythema, skin ulceration, subcutaneous calcinosis, Mechanic's hands, myalgia, interstitial lung disease, pulmonary arterial hypertension), laboratory, immunological [anti-autoantibodies including melanoma differentiation associated gene 5 (anti-MDA5), anti-Mi-2, anti-transcription intermediary factor-1γ (anti-TIF-1γ, anti-nuclear matrix protein 2 (anti-NXP2), anti-small ubiquitin-like modifier activating enzyme (anti-SAE), anti-synthetase], imaging and therapeutic status data of the patients at the diagnosis of myositis with and without thromboembolism were collected and the differences in these data were analyzed. Logistic regressive analysis was used to identify the risk factors of thromboembolism. RESULTS: In the retrospective study, 390 myositis patients were investigated. The mean age of onset was (49.6±13.4) years, male to female ratio was 0.31 :1. Thromboembolism was identified in 4.62% (18/390) of the myositis patients, which was lower than the published reports. Out of 18 patients with thromboembolism, 55.6% (10/18) of them were deep venous thrombosis, followed by cerebral infarction (22.2%, 4/18), pulmonary embolism (11.1%, 2/18), renal artery embolism (5.6%, 1/18) and embolism of upper extremity (5.6%, 1/18). Fifty percent of thromboembolism events occurred 6 months after the diagnosis of myositis, 38.9% of thromboembolism events occurred 6 months within the diagnosis of myositis, 11.1% of thromboembolism events occurred 6 months before the diagnosis of myositis. As compared with the myositis patients without thromboembolism, the myositis patients complicated with thromboembolism were older [(58.3±11.7) years vs. (49.3±13.4) years, P=0.006]. C-reaction protein (CRP) (12.2 mg/L vs. 4.1 mg/L, P < 0.001), ferritin (20 085.5 µg/L vs. 216.6 µg/L, P < 0.001) and D-dimer (529.0 µg/L vs. 268.0 µg/L, P=0.002) were significantly higher in thromboembolism group. Diabetes (44.4% vs. 16.4%, P=0.006), coronary heart disease (22.2% vs. 3.0%, P=0.003) and surgery (16.7% vs. 3.5%, P=0.032) were observed more common in thromboembolism group than those without thromboembolism. Activated partial thromboplastin time (APTT) (26.9 s vs. 28.7 s, P=0.049) and albumin (32.4 g/L vs. 36.5 g/L, P=0.002) was lower in thromboembolism group. The risk factors of thromboembolism in the myositis patients were low level of albumin (OR=0.831, 95%CI: 0.736-0.939, P=0.003), diabetes (OR=4.468, 95%CI: 1.382-14.448, P=0.012), and coronary heart disease (OR=22.079, 95%CI: 3.589-135.837, P=0.001) were independent significant risk factors for thromboembolism in the patients with myositis. There was no significant difference in clinical manifestations, myositis-specific antibodies or myositis-associated antibodies between the two groups. CONCLUSION: Thromboembolism is a complication of myositis. Lower levels of albumin, diabetes, and coronary heart disease might be risk factors of thromboembolism in myositis patients.

[Long-term prognostic value of mean platelet volume in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention].

Objective: To evaluate the relationship between admission mean platelet volume (MPV) and 2-year cardiac mortality in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI), and explored the consistence of this relationship in diabetes mellitus (DM) and non-DM subgroups. Method: A total of 4 293 patients who underwent PCI in Fuwai Hospital in 2013 were enrolled and divided into two groups according to MPV as follows: lower MPV (n=2 219, MPV≤10.5fL) and higher MPV (n=2 074, MPV>10.5fL). Result: Patients with high MPV had a higher rate of DM (30.4%(674/2 219) vs 34.5%(715/2 074)), smoking (53.3%(1 183/2219) vs 57.0%(1 182/2 074)), and previous coronary artery bypass grafting (CABG) (4.0%(88/2 219) vs 5.4%(112/2 074)), while left ventricular ejection fraction (LVEF) (64±7 vs 63±7), and glomerular filtration rate (eGFR) (92±14 vs 91±15) were lower compared with patients in the low MPV group (all P<0.05). In the laboratory examination, patients with high MPV had higher glycosylated hemoglobin, and lower platelet count (all P<0.05). In coronary angiography, there was no significant difference in SYNTAX scores, left main/three-vessel lesions, stent type, success rate of operation, and total stent length (all P>0.05). Compared with low MPV group, patients with high MPV had ahigher cardiac mortality [18 (0.9%) vs 5 (0.2%), P=0.004]. Kaplan-Meier analysis showed that compared to low MPV group, cardiac mortality in high MPV group was significantly higher (Log-rank P=0.004). Multivariate Cox regression analysis showed that high MPV was independently associated with 2-year cardiac mortality (HR 4.127, 95%CI 1.373 to 12.405, P=0.012). Receiver operating characteristic curve (ROC) analysis also showed that MPV had a good diagnostic value in predicting 2-year cardiac mortality (area under the curve=0.624, 95%CI: 0.511-0.738, P=0.04). Subgroup analysis showed that in patients with DM (HR 2.090, 95%CI 1.217-3.589, P=0.008) and male (HR 1.561, 95%CI 1.007-2.421, P=0.047), MPV was significantly related with cardiac mortality. Conclusion: In patients with stable CAD who underwent elective PCI, high MPV was independently associated with an increase in 2-year cardiac mortality, especially in patients with DM and male gender.

[The impact of metabolic syndrome and its individual components on long-term prognosis of patients undergoing percutaneous coronary intervention].

Objective: To investigate the impact of metabolic syndrome (MS) and its individual components on long-term prognosis of patients undergoing percutaneous coronary intervention(PCI). Methods: Patients who underwent PCI in Fuwai Hospital in 2013 were enrolled and divided to two groups: with MS and without MS. The primary endpoint of 2-year follow-up was major adverse cardiovascular events (MACE), including death, myocardial infarction, and repeat revascularization. Results: Of the 10 422 PCI patients, there were 5 656 (54.27%) without MS and 4 766 (45.73%) with MS. Patients in the MS group were younger, tended to be male and had more comorbidities. There were no significant differences between the two groups in the proportion of drug-coated stents and the success rate of interventional therapy. The 2-year follow-up showed that the incidence of MACE in the MS group was significantly higher than that in the MS-free group (12.0% vs 10.0%, P<0.001), which was mainly due to the significantly higher revascularization rate in the MS group than in the non-MS group (9.5% vs 7.9%, P=0.003). Cox's regression analysis showed that MS was an independent risk factor for MACE. In MS component analysis, abnormal glucose metabolism was an independent risk factor for MACE events. Conclusions: Among the patients undergoing PCI, the incidence of MACE in patients with MS is significantly higher than that in patients without MS, and MS was an independent risk factor for MACE. In addition, hyperglycemia is an independent predictor for MACE.

[Impact of coronary artery lesion calcification on the long-term outcome of patients with coronary heart disease after percutaneous coronary intervention].

Objective: To investigate the impact of coronary lesion calcification on the long-term outcome of patients with coronary heart disease after percutaneous coronary intervention. Methods: In this prospective observational study, a total of 10 119 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention from January 1 to December 31, 2 103 in our hospital were enrolled. The patients were divided into non/mild calcification group (8 268 cases) and moderate/severe calcification group (1 851 cases) according to the angiographic results. The primary endpoint was one-year major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, and target vessel revascularization. Results: The patients were (58.3±10.3) years old, and there were 2 355 females (23.3%). Compared with non/mild calcification group, patients in the moderate/severe calcification group were older ((60.0±10.6) years vs. (57.9±10.2) years, P<0.01), and had higher proportion of female (25.4% (470/1 851) vs. 22.8% (1 885/8 268), P=0.02), debates (33.9% (628/1 851) vs. 29.0% (2 399/8 268), P<0.01), hypertension (68.0% (1 259/1 851) vs. 63.7% (5 264/8 268), P<0.01), coronary artery bypass grafting (4.6% (85/1 851) vs. 3.2% (268/8 268), P<0.01), stroke (12.6% (233/1 851) vs. 10.4% (861/8 268), P=0.01), and renal dysfunction (6.2% (115/1 851) vs. 3.7% (303/8 268), P<0.01). Compared with non/mild calcification group, patients in themoderate/severe calcification group experienced longer procedure time (37 (24, 61) min vs. 27 (17,40) min, P<0.01) and stent length was longer (32 (23,48) mm vs. 27 (18,38) mm, P<0.01), and percent of rotational atherectomy was higher (2.56%(57/2 229) vs. 0.03% (3/11 930), P<0.01). One-year follow-up results showed that MACE (7.5% (139/1 846) vs. 4.9% (402/8 243), P<0.01), all-cause death (1.0% (19/1 846) vs. 0.6% (49/8 243), P=0.04), myocardial infarction (2.2% (41/1 846) vs. 1.4% (114/8 243), P=0.01), and target vessel revascularization (5.0% (92/1 846) vs. 3.2% (266/8 243), P<0.01) were all significantly higher in moderate/severe calcification group than in non/mild group. Multivariate Cox regression analysis showed that moderate/severe calcification was an independent predictor of MACE at one-year after the procedure (HR=1.41, 95%CI 1.16-1.72, P<0.01). Conclusion: Moderate/severe calcification in coronary lesion is an independent predictor of long-term poor prognosis in coronary heart disease patients undergoing percutaneous coronary intervention.

[Predictive value of neutrophil to lymphocyte ratio on long-term outcomes of acute myocardial infarction patients with multivessel disease].

Objective: Patients with acute coronary syndrome due to multivessel disease (MVD) were at the highest risk of adverse cardiovascular events. Neutrophil to lymphocyte ratio (NLR) was proposed as a marker of cardiovascular risk. Present study evaluated the independent predictive value of NLR for acute myocardial infarction (AMI) patients with MVD. Methods: AMI patients with MVD (n=1 433) underwent percutaneous coronary intervention (PCI) between January 2013 and December 2013 were followed up for 2 years. Patients were divided into 2 sub-groups based on an optimal cut off value of NLR to predict 2-year all-cause mortality. The primary endpoint was all-cause death. The secondary endpoint was long-term major adverse cardiovascular and cerebrovascular events (MACCE). Results: By receiver operating characteristics curve analysis, the optimal cut-off value of admission NLR to predict 2-year all-cause mortality was 3.39 (area under the curve 0.765, sensitivity 71%, specificity 73%). The high NLR group(n=396) had higher prevalence of prior myocardial infarction, prior PCI and intra-aortic balloon pump use (IABP)(P<0.01). Compared to the low NLR group (n=1 037), patients in the high NLR group were older, had higher level of neutrophil count and high-sensitivity C-reactive protein (hs-CRP) (P<0.001), but lower level of lymphocyte count, estimated glomerular filtration rate (eGFR) and ejection fraction (P<0.001). During the follow-up period, rate of long-term all-cause death was significantly higher in the high NLR group than in the low NLR group (5.1% (20/396) vs. 0.8% (8/1 037), P<0.001). Cardiac death (4.0% (16/396) vs. 0.7% (7/1 037), P<0.001) and MACCE (21.7% (86/396) vs. 12.6% (131/1 037), P<0.001) were also significantly higher in the high NLR group than in the low NLR group. Multivariate Cox analysis showed that NLR ≥ 3.39 was determined as an independent predictor of 2-year all-cause mortality (HR=3.23, 95%CI 1.38-7.54, P=0.007) and MACCE (HR=1.58, 95%CI 1.19-2.10, P=0.002) in this patient cohort after adjusting for other risk factors. Correlation analysis showed that the NLR was positively correlated with hs-CRP levels (r=0.241, P<0.001). Conclusion: Our study demonstrates that admission NLR ≥ 3.39 is an independent predictor of long term all cause death and MACCE in AMI patients with MVD post PCI.

[Clinical characteristics and prognosis between male and female patients with premature coronary artery disease after intervention].

Objective: To compare the clinical characteristics and long-term prognosis between male and female patients with premature coronary artery disease (PCAD) post coronary intervention, and analyse the risk factors of major adverse cardio-cerebrovascular events (MACCE) and bleeding events. Methods: This was a prospective single-center observational study. From January 2013 to December 2013, 4 744 patients diagnosed as PCAD and treated with percutaneous coronary intervention (PCI) in Fuwai Hospital were enrolled. The general clinical data, laboratory results and interventional treatment data of all patients were collected, and patients were followed up for 2 years after PCI and the incidence of events including MACCE and bleeding was analyzed. The baseline data and clinical events of PCAD patients of different genders were compared. Survival curves were estimated by Kaplan-Meier method. Univariate and multivariate Cox regression were used to analyze whether gender was an influencing factor of different clinical events of PCAD patients within 2 years after PCI, and other relevant influencing factors of MACCE and bleeding events. Results: Among the 4 744 PCAD patients included, there were 3 390 (71.5%) male aged (47.0±5.4) years old and 1 354 (28.5%) female aged (57.0±5.8) years old. Compared with female patients, male patients had higher body mass index, higher proportion of hyperlipidemia, smoking, myocardial infarction, previous PCI, preoperative estimated glomerular filtration rate, ST-segment elevation myocardial infarction, radial artery approach, intravenous ultrasound use and chronic occlusive lesions (all P<0.05). Age, left ventricular ejection fraction, prevalence of hypertension, diabetes mellitus, past stroke history, non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and the use of calcium channel blockers were lower in male patients than in female patients (all P<0.05). The 2-year follow-up results showed that the incidence of BARC type 1 hemorrhage was significantly higher in female patients than in male patients (6.9%(92/1 343) vs. 3.7%(126/3 378), P<0.001); however, the incidence of MACCE, all-cause death, cardiac death, recurrent myocardial infarction, revascularization (target vessel revascularization and target lesion revascularization), stent thrombosis, stroke and BARC type 2-5 hemorrhage were similar between the two groups (all P>0.05). Multivariate Cox regression analysis showed that gender was an independent risk factor for BARC type 1 bleeding in PCAD patients (HR=2.180, 95%CI 1.392-3.416, P<0.001), but it was not an independent risk factor for MACCE and BARC type 2-5 bleeding(all P>0.05). Hyperlipidemia, preoperative SYNTAX score, multivessel lesions and NSTE-ACS were the independent risk factors for MACCE in PCAD patients with PCI (the HRs(95%CI) were 1.289(1.052-1.580), 1.030(1.019-1.042), 1.758(1.365-2.264), 1.264(1.040-1.537), respectively); gender (HR=1.579, 95%CI 1.085-2.297, P=0.017), hyperlipidemia (HR=1.305, 95%CI 1.005-1.695, P=0.046), anticoagulant drugs including low molecular weight heparin (HR=1.321, 95%CI 1.002-1.741, P=0.048) or sulfonate(HR=1.659, 95%CI 1.198-2.298, P=0.002) were the independent risk factors for bleeding events. Conclusions: There are differences in clinical and coronary artery lesion characteristics between different genders in patients with PCAD. The incidence of minor bleeding is significantly higher in female PCAD patients than in male PCAD patients. Hyperlipidemia, preoperative SYNTAX score, multivessel lesions and NSTE-ACS are the independent risk factors for MACCE, and gender, hyperlipidemia, anticoagulant drugs including low molecular weight heparin or sulfonate are the independent risk factors for bleeding events in patients with PCAD.

[Impact of short-time anticoagulant therapy after selective percutaneous intervention on prognosis of patients with coronary artery disease].

Objective: To observe the safety and impact of short-term anticoagulant therapy on prognosis after selective percutaneous coronary intervention (PCI) in patients with coronary artery disease. Methods: From January 2013 to December 2013, 9 769 consecutive patients underwent selective PCI in Fuwai Hospital were retrospectively included in this study. Patients were divided into two groups, including non-post-PCI anticoagulant therapy group and low-dose and short-time post-PCI anticoagulant therapy group (enoxaparin 0.4 ml/12 h or fondaparinux 2.5 mg/day by subcutaneous injection for 2-3 days after PCI). All patients were evaluated at 30 days, 180 days and 12 months for major adverse coronary and cerebral events (MACCE) including all-cause death, myocardial infarction, revascularization and stroke as well as in-stent thrombosis and bleeding events. Data from 1 755 pairs of patients were analysis after propensity score matching. The clinical outcomes were compared between groups by using Kaplan-Meier survival analysis before and after propensity score matching. Multivariable Cox analysis was used to define the impact and determinants of post-PCI anticoagulation on clinical outcomes. Results: one thousand seven hundred and fifty-five (18.0%) patients didn't receive post-PCI anticoagulation and 8 014 (82.0%) patients received post-PCI anticoagulation, 5 666 (58.0%) patients received enoxaparin and 2 348 (24.0%) patients received fondaparinux. Patients were younger and incidence of female patients was less, incidence of renal dysfunction and acute coronary syndrome were higher in low-dose and short-time post-PCI anticoagulant therapy group than in non-post-PCI anticoagulation group (all P<0.05). Similarly, patients with post-PCI anticoagulation were associated with more left main coronary artery lesion and branch lesion (P<0.05). Post-PCI anticoagulation patients were associated with less trans-femoral process, more drug-eluting stents implantation and less simple balloon dilatation (all P<0.05). Nine thousand seven hundred and seventeen (99.5%) patients completed 2 years follow up. Post-PCI anticoagulation patients had significantly lower 30-day all-cause death (0.05% (4 cases) vs. 0.46% (8 cases), P<0.001) and stroke (0 vs. 0.11% (2 cases), P=0.003), lower 180-day all-cause death (0.17% (14 cases) vs. 0.57% (10 cases), P=0.002), revascularization (2.07% (166 cases) vs. 3.71% (65 cases), P<0.001) and MACCE (3.49% (280 cases) vs. 5.47% (96 cases), P<0.001), lower 2-year revascularization (7.61% (610 cases) vs. 12.84% (225 cases), P<0.001) and MACCE (10.92 (875 cases) vs. 16.01% (281 cases), P<0.001). Multivariable Cox regression analysis showed that post-PCI anticoagulant therapy was an independent protective factor of 30-day (HR=0.17, 95%CI 0.05-0.62, P=0.007), 180-day all-cause death (HR=0.37, 95%CI 0.16-0.87, P=0.023) and MACCE (HR=0.74, 95%CI 0.58-0.94, P=0.013), 2-year MACCE (HR=0.71, 95%CI 0.62-0.81, P<0.001). After propensity score matching, post-PCI anticoagulation therapy remained as an independent protective factor of 30-day all-cause death (HR=0.11, 95%CI 0.01-0.92, P=0.042) and 2-year MACCE (HR=0.81, 95%CI 0.68-0.96, P=0.015). Conclusions: Low-dose and short-time post-PCI anticoagulant therapy may decrease 30-day all-cause death, 180-day all-cause death and MACCE and 2-year MACCE, and meanwhile this option does not increase bleeding risk in patients underwent selective PCI.

[Doxycycline inhibits paraquat-induced pulmonary fibrosis via TGF-ß1/Smad pathway].

Objective: To investigate the possible mechanism of doxycycline inhibiting paraquat-induced pulmonary fibrosis and provide a theoretical basis for its clinical application. Methods: Human lung fibroblast HFL1 cells were selected as the research object in the cell group. Divided into blank group, paraquat group, paraquat+doxycycline group. The expression of TGF-ß1, a-SMA, Smad3 and Smad2 protein was detected by ELISA using 40 ml of paraquat 40 umol/L and 3 mg/L of oleic acid 10 mg/L. In the animal group, 120 healthy and clean SD rats were randomly divided into three groups: blank group, paraquat group, paraquat+doxycycline group. The expression of TGF-ß1, a-SMA, Smad3 and Smad2 protein in lung tissue of mice at 1 day, 3 days, 7 days, 14 days and 21 days was detected by Elisa method. The expression of TGF-ß1, a-SMA, Smad3 and Smad2 protein in lung tissue of 21-day mice was detected by Western Blotting. The pathological changes of lung tissue were observed by HE staining for 1 day, 3 days, 7 days, 14 days and 21 days. Results: In the cell group experiment, the expression of TGF-ß1, a-SMA, Smad3 and Smad2 protein increased gradually with paraquat in the paraquat group, and the expression of TGF-ß1, a-SMA, Smad3 and Smad2 protein was significantly higher than that in the blank group. The difference was statistically significant (P<0.05) . The expressions of TGF-ß1, a-SMA, Smad3 and Smad2 in the paraquat+doxycycline group were significantly lower than those in the paraquat group, but still higher than the blank group, the difference was statistically significant (P<0.05) . Conclusion: Doxycycline inhibits paraquat-induced pulmonary fibrosis by inhibiting the expression of TGF-ß1, a-SMA and Smad3, Smad2 proteins.

Bombyx mori cyclin-dependent kinase inhibitor is involved in regulation of the silkworm cell cycle.

Cyclin-dependent kinase inhibitors (CKIs) are negative regulators of the cell cycle. They can bind to cyclin-dependent kinase (CDK)-cyclin complexes and inhibit CDK activities. We identified a single homologous gene of the CDK interacting protein/kinase inhibitory protein (Cip/Kip) family, BmCKI, in the silkworm, Bombyx mori. The gene transcribes two splice variants: a 654-bp-long BmCKI-L (the longer splice variant) encoding a protein with 217 amino acids and a 579-bp-long BmCKI-S (the shorter splice variant) encoding a protein with 192 amino acids. BmCKI-L and BmCKI-S contain the Cip/Kip family conserved cyclin-binding domain and the CDK-binding domain. They are localized in the nucleus and have an unconventional bipartite nuclear localization signal at amino acid residues 181-210. Overexpression of BmCKI-L or BmCKI-S affected cell cycle progression; the cell cycle was arrested in the first gap phase of cell cycle (G1). RNA interference of BmCKI-L or BmCKI-S led to cells accumulating in the second gap phase and the mitotic phase of cell cycle (G2/M). Both BmCKI-L and BmCKI-S are involved in cell cycle regulation and probably have similar effects. The transgenic silkworm with BmCKI-L overexpression (BmCKI-L-OE), exhibited embryonic lethal, larva developmental retardation and lethal phenotypes. These results suggest that BmCKI-L might regulate the growth and development of silkworm. These findings clarify the function of CKIs and increase our understanding of cell cycle regulation in the silkworm.

[Predictive value of GRACE discharge score for long-term out-of-hospital death in acute coronary syndrome after percutaneous coronary intervention].

Objective: To evaluate the prognostic value of Global Registry of Acute Coronary Events(GRACE) discharge score for long-term out-of-hospital death in acute coronary syndrome (ACS) after drug-eluting stents (DES) and with Dual-antiplatelet Therapy (DAPT). Methods: Our study was a prospective, observational, single center (Fuwai Hospital of China) study.A total of 6 431consecutive ACS patients underwent percutaneous coronary intervention(PCI)between January 2013 and December 2013 were involved.The primary endpoint was all-cause death and second endpoint was major adverse cardiovascular and cerebrovascular events (MACCE) as a composite of all-cause death, myocardial infarction, revascularization, stent thrombosis or stroke. Results: Finally, 5 867 ACS patients who were received DES with DAPT and had no in-hospital event included in this study, and 59 (1.01%) death and 608 (10.36%) MACCE were reported during 2-year follow-up after discharge.GRACE score was significantly higher among death patients than those survivalpatients (94± 28 vs 78± 24, P<0.001). According to risk stratification of GRACE discharge score, as compared to the low-risk group, death risk in high-risk group was 6.73 times (HR=6.73, 95%CI 3.53-12.84; P<0.001) higher, but could not distinguish between the moderate and low risk group (HR=1.61, 95%CI 0.88-2.95; P=0.124). The GRACE score showed predictive value in ACS patients after DESand with DAPT (area under the receiver operating characteristic curve (AUROC)=0.661; 95%CI 0.586-0.736, P<0.001). In subgroup analysis, GRACE score also showed predictive value both in unstable angina pectoris (UAP)(AUROC=0.660, 95%CI 0.576-0.744; P<0.001) and acute myocardial infarction(AMI)subgroup (AUROC=0.748, 95%CI 0.631-0.864; P=0.001). Conclusion: GRACE discharge score shows prognostic value for long-term out-of-hospital death in ACS patients undergoing PCI with DES and DAPT, and demonstrates good risk stratification of high and low-risk of death.

[Long-term prognosis of coronary artery disease with atrial fibrillation after percutaneous coronary intervention].

Objective: To investigate the long-term prognosis of coronary artery disease with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Methods: A total of 10 724 patients with PCI were enrolled in 2013, and 2-year clinical outcomes in patients with AF (AF group) and without AF (non-AF group) were compared. Results: A total of 113 patients were with AF (1.1%), and 8 out of them were on triple antithrombotic therapy (9.5%), and AF group patients were with more complications. The 2-year follow-up results showed that the all-cause mortality in AF group was significantly higher than that in non-AF group (9.7% vs 1.1%; P<0.001). The incidence of cardiac death, stent thrombosis and stroke was also significantly higher in patients with AF. The incidence of major adverse cardiac and cerebrovascular events (MACCE) was also significantly higher in AF group compared with non-AF group (17.7% vs 8.8%; P<0.001), whereas the incidence of revascularization was significantly lower in the AF group than in the non-AF group (2.7% vs 8.7%; P=0.023). The incidence of myocardial infarction and bleeding had no significant difference between the two groups, and the adverse events between the two groups had no significant difference after propensity score (PS) either. Conclusions: The 2-year clinical follow-up of single-center, large-sample PCI patients shows poor prognosis in patients with AF compared with the non-AF patients. But there is no difference in the prognosis between the two groups after PS, however, this conclusion still needs to be confirmed by randomized controlled studies.

[Safety and efficacy of second generation drug eluting stents in diabetic and non-diabetic patients].

Objective: To investigate the long-term prognosis of Second generation drug-eluting stents(G2-DES) in diabetic mellitus(DM) and non-DM patients. Methods: Patients with coronary heart disease(CHD) in Fuwai Hospital from January 2013 to December 2013 who had exclusively G2-DES implantation, were consecutively included the follow-up period was 2 years. Results: A total of 6 094 patients with CHD were implanted with G2-DES, of which 1 862 patients with DM, and 4 232 patients without DM.The proportion of DM patients receiving G2-DES implantation with the following characteristics: advanced age, female, hypertension, hyperlipidemia, history of previous stroke, history of peripheral artery disease, previous history of PCI, and with triple vessel, high preoperative Syntax score, high number of target lesions, B2 or C type lesions, severe calcification lesions, and chronic occlusive disease were significantly higher than those of non-DM patients(P<0.05). The incidence of major adverse cardiac and cerebral vascular events(MACCE), target vascular revascularization(TVR) and target lesion revascularization(TLR) were higher in DM patients than in non-DM patients during 2 year's follow-up(P<0.05). The univariate COX regression analysis showed that diabetes was risk factor for MACCE in patients with CHD implanting G2-DES(HR=1.241, 95%CI: 1.053-1.463, P=0.010). However, multivariable COX analysis showed that DM was not an independent risk factor for MACCE in CHD patients with G2-DES(HR=1.125, 95%CI: 0.952-1.330, P=0.167). While age, female, preoperative Syntex score, triple vessel, B2 or C lesion were independent risk factors for poor clinical prognosis in CHD patients with G2-DES. Conclusions: (1) CHD patients with DM often accompany more clinical risk factors and complicated coronary lesions; (2) the incidence of MACCE, TVR and TLR in DM patients is significantly higher than non-DM patients with G2-DES during the 2 year's follow-up; (3) after multivariate adjustment, DM is not an independent risk factor for poor clinical prognosis in CHD patients with G2-DES, while traditional risk factors and complex coronary lesions are independent risk factors for poor clinical prognosis.

[Impact of high-sensitivity C-reactive protein on outcomes in patients with acute coronary syndrome undergoing drug-eluting stent implantation].

Objective: To investigate the association between high-sensitivity C-reactive protein (hs-CRP) and long-term outcomes in Chinese patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after drug-eluting stent (DES) implantation. Methods: A total of 4 815 consecutive NSTE-ACS patients who treated with DESs were included.Patients were divided into three groups: <1.00 mg/L, 1.00 to 2.99 mg/L and ≥3.00 mg/L, based on the level of hs-CRP on admission.Major adverse cardiovascular and cerebrovascular events (MACCE, including all-cause death, myocardial infarction, revascularization, in-stent thrombosis and stroke) were compared among groups during 2-year follow-up. Results: Patients with higher hs-CRP had more risk factors of cardiovascular events such as concomitant morbidities and multi-vessel lesions(68.5% vs 73.6% vs 76.2%, P<0.001). Higher hs-CRP value was associated with increased rates of MACCE (8.8% vs 11.2% vs 12.6%, P=0.003) and revascularization (6.5% vs 8.5% vs 9.8%, P=0.003). However, the rates of all-cause death, myocardial infarction, stroke, and stent thrombosis were comparable among groups(all P>0.05). Ongoing divergences in MACCE and revascularization among three groups were significant on Kaplan-Meier curves (both Log-rank P=0.003). Multivariable Cox regression analysis indicated that compared to hs-CRP<1.00 mg/L group, MACCE in the >3.00 mg/L group was increased by 42% [HR 1.42 (1.13-1.78), P=0.002]. Meanwhile, multivessel leisions, ejection fraction<50%, elevated white blood cell counts were also independent risk factors.CRP≥3.00 mg/L(HR 1.56, 95%CI 1.16-2.08, P=0.003, compared to <1.00 mg/L) and multivessel leisions were independent predictors of revascularization. Conclusions: (1)Patients with higher hs-CRP on admission have more risk factors of cardiovascular events.(2)Higher hs-CRP value is associated with increased rates of MACCE and revascularization.(3)Pre-procedural hs-CRP is an independent predictor of 2-year outcomes for Chinese NSTE-ACS patients treated with DESs.

[Clinical outcomes with beta-blockers in stable patients undergoing percutaneous coronary intervention with adequate left ventricular ejection function].

Objective: To investigate the impact of beta-blockers on long-term outcomes in patients who underwent percutaneous coronary intervention (PCI) for stable coronary artery disease (SCAD) with adequate left ventricular ejection function (LVEF). Methods: A total of 3 946 consecutive SCAD patiens who underwent PCI with adequate LVEF between January and December 2013 in Fuwai Hospital were prospectively included in this study. According to beta-blocker use at discharge, patients were divided into no-beta-blocker group (n=309) and beta-blocker group (n=3 637). Major adverse cardiovascular and cerebrovascular events (MACCE) including all-cause death, myocardial infarction, revascularization, stroke and stent thrombosis at 2 years were compared between the two groups. Multivariate Cox regression analysis and Propensity-score matched analysis were used to identify independent risk factors of poor prognosis. Results: Compared with those in the beta-blocker group, patients of no-beta-blocker group were more likely to have lower body mass index, less complex comorbidities, slower heart rate either on admission or at discharge. There was no significant association of beta-blocker use with 2-year mortality (0.8% versus 1.3%, hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.23 to 1.86, P=0.421), myocardial infarction ( HR 0.66, 95% CI 0.24 to 2.64, P=0.718) or MACCE (HR 0.70, 95% CI 0.65 to 1.32, P=0.674). Results were similar in propensity score-matched analysis. Conclusions: In this large, prospective, single-center study, patients with beta-blocker prescription appear to have more risk factors. No beta-blockers at discharge is not an independent risk factor of poor prognosis at up to 2 years among stable patients who underwent PCI with adequate LVEF.

[Relationship between thrombolysis in myocardial infarction risk index and the severity of coronary artery lesions and long-term outcome in acute myocardial infarction patients undergoing percutaneous coronary intervention].

Objective: To investigate the relationship between thrombolysis in myocardial infarction risk index(TRI) and the severity of coronary artery lesions and long-term outcome in acute myocardial infarction(AMI) patients undergoing percutaneous coronary intervention(PCI). Methods: A total of 1 663 consecutive AMI patients undergoing PCI between January and December 2013 in Fuwai hospital were prospectively included in this study. The severity of coronary artery lesions was evaluated using the SYNTAX score. Receiver operating characteristic(ROC) curve was used to analyze the optimal cut-off value of TRI on predicting all-cause mortality at 2 years after PCI.The patients were divided into 2 groups based on the optimal cut-off value of TRI:high TRI group (TRI ≥ 23.05, 465 cases) and low TRI group(TRI<23.05, 1 198 cases). Multivariate logistic regression analyses were used for determining the relationship between TRI and SYNTAX scores≥33. A multivariate Cox regression analyses was used to identify the influence factors of long-term outcome after PCI. Results: SYNTAX score was higher in high TRI group than in low TRI group (13.00(7.00, 20.50) vs.10.25(7.00, 17.00), P<0.001). TRI was independently associated with SYNTAX score ≥ 33 (OR=1.09,95% CI 1.03-1.16, P=0.004). After the 2 years follow-up, rates of all-cause death (4.1% (19/465) vs. 0.3% (4/1 198) , P<0.001), cardiac death (2.6% (12/465) vs. 0.2% (2/1 198) , P< 0.001) and stent thrombosis (1.7% (8/465) vs. 0.5% (6/1 198) , P=0.015) were all significantly higher in high TRI group than in low TRI group. Multivariate Cox regression analyses showed that TRI≥ 23.05 was an independent risk factor of all-cause death (HR=5.22, 95%CI 1.63-16.72, P=0.005), cardiac death (HR=8.48, 95%CI 1.75-41.07, P=0.008) and stent thrombosis(HR=3.87, 95%CI 1.32-11.41, P=0.014) at 2 years after PCI in AMI patients, but which was not the independent risk factor of major adverse cardiovascular and cerebrovascular events (HR=0.96, 95%CI 0.69-1.36, P=0.834) .The area under ROC curve of TRI ≥ 23.05 on predicting 2 years all-cause mortality in AMI patients undergoing PCI was 0.803(95%CI 0.711-0.894, P<0.001). Conclusions: TRI is independently associated with SYNTAX score ≥ 33. TRI is also an independent risk factor of 2 years all-cause death, cardiac death and stent thrombosis in AMI patients undergoing PCI.

[Predictive value of the GRACE discharge score on the long-term out-of-hospital coronary thrombotic events after implantation of drug-eluting stents].

Objective: To evaluate the predictive value of GRACE discharge score on the long-term out-of-hospital coronary thrombotic events (CTE) after percutaneous coronary intervention (PCI) with drug-eluting stents. Methods: Present study was a prospective, observational, single center study. 10 724 consecutive patients underwent PCI in Fuwai Hospital between January and December 2013 were included, stents were implanted with conventional method. After PCI, patients were prescribed aspirin 100 mg once daily indefinitely, and either clopidogrel 75 mg once daily or ticagrelor 90 mg twice daily for at least 1 year. A total of 9 782 patients were included in the final analysis after excluding patients who did not undergo successful stent implantation, who were not discharged on dual anti-platelet therapy (DAPT), who only underwent bare-metal stents, who experienced in-hospital major bleeding, stent thrombosis, myocardial infarction (MI) or death,and who lost follow up. Clinical data were collected from all patients. 9 543 patients with complete baseline data were further analyzed for risk stratification and predictive value of GRACE discharge score. CTE was defined as stent thrombosis or spontaneous myocardial infarction. All patients were followed through Fuwai Hospital Follow-up Center, and evaluated either by phone, letter, or clinic visits or at 1, 6, 12 and 24 months after PCI. Risk stratification was performed according to the GRACE discharge score, and the predictive value of the GRACE discharge score was assessed using the receiver operating characteristic (ROC) curve. Results: After 2 years follow-up, there were 95 CTE among the 9 782 patients. The patients were divided into 2 groups according to the presence or absence of CTE: CTE group (95 cases) and no CTE group (9 687 cases). GRACE discharge score was significantly higher in CTE group than no CTE group (82.98±27.58 vs. 75.51±22.46, t=-2.57, P=0.012). According to risk stratification of GRACE discharge score, the patients were divided into low-risk (≤88) group (n=6 902), moderate-risk (89-118) (n=2 988) and high-risk (>118) (n=343) groups. As compared to the low-risk group, CTE risk in moderate- and high-risk groups was 1.59 times (HR 1.59, 95%CI 1.01-2.52, P=0.046) and 3.89 times higher (HR 3.89, 95%CI 1.98-7.65, P<0.001), respectively. Further analysis showed that the GRACE score had predictive value in the total cohort for CTE (area under the receiver operating characteristic (AUROC) 0.576, 95%CI 0.512-0.640, P=0.012) and in the acute coronary syndromes(ACS) subgroup for CTE: (AUROC 0.594, 95%CI 0.509-0.680, P=0.019), but not in the non-ACS subgroup: (AUROC 0.561, 95%CI 0.466-0.657, P=0.187). Conclusion: GRACE discharge score can predict the long-term out-of-hospital CTE in patients undergoing PCI with drug-eluting stents and treated with DAPT, and patients can be stratified into the low-, moderate- and high-risk groups of CTE by the GRACE discharge score.

[Impact of direct bilirubin on the long-term outcome of patients with acute coronary syndrome post percutaneous coronary intervention].

Objective: To investigate the impact of direct bilirubin on long-term prognosis of acute coronary syndrome (ACS) patients post percutaneous coronary intervention(PCI). Methods: As a prospective and observational cohort study, a total of 6 431 consecutive ACS patients underwent PCI from January to December 2013 in Fuwai hospital were included. Patients were divided into 3 groups according to tertiles values of direct bilirubin as follows: low direct bilirubin group(<2.2 µmol/L, n=2 219), moderate direct bilirubin group(2.2-3.0 µmol/L, n=2 016), and high direct bilirubin group(>3 µmol/L, n=2 196). The clinical characteristics were compared among the 3 groups, and the impact of direct bilirubin on clinical adverse events (main adverse cardiovascular and cerebrovascular events included cardiogenic death, myocardial infarction, revascularization, stroke, and stent thrombosis) were analyzed at 2 years after PCI. Results: (1) Percent of male patients was 66.5%(1 475/2 219), 78.0%(1 572/2 016), and 86.2%(1 892/2 196), body mass index was(25.7±3.1), (26.0±3.3),and (26.0±3.2) kg/m(2), the ratio of the history of old myocardial infarction was 11.9%(264/2 219), 13.0%(263/2 016),and 14.9%(328/2 196), the ratio of the current smoker was 56.3%(1 249/2 219), 59.1%(1 192/2 016),and 60.0%(1 317/2 196) in low, moderate and high direct bilirubin groups respectively, and the differences were statistically significant (P<0.01 or 0.05). (2) Two years after PCI, the all-cause mortality was 0.8%(17/2 219), 1.8%(36/2 016), and 1.5%(33/2 196) (P=0.011),the cardiogenic mortality was 0.5%(12/2 219), 1.3%(26/2 016), and 0.6%(13/2 196) (P=0.010),the ratio of myocardial infarction was 2.2%(49/2 219), 2.4%(49/2 016), and 1.4%(31/2 196)(P=0.044),the ratio of revascularization was 8.8%(195/2 219), 8.3%(168/2 016),and 8.9%(196/2 196)(P=0.783),the ratio of stroke was 1.4%(30/2 219),1.1%(22/2 016), and 1.9%(42/2 196)(P=0.076),the ratio of stent thrombosis was 0.9%(19/2 219), 1.2%(24/2 016),and 0.7%(15/2 196)(P=0.210) in low, moderate and high direct bilirubin groups, respectively. (3) Multivariable Cox regression analysis showed that, patients in moderate direct bilirubin group faced increased the risk of all-cause mortality compared with patients in the low direct bilirubin group (HR=2.23, 95%CI 1.23-4.05, P= 0.009), and the risk of all-cause mortality was similar between high direct bilirubin group and low direct bilirubin group (HR=1.84, 95%CI 0.99-3.38, P= 0.051). There were no statistically significant difference in the risks of main adverse cardiovascular and cerebrovascular events,cardiogenic death, myocardial infarction, revascularization, stroke, and stent thrombosis in moderate and high direct bilirubin groups compared with low direct bilirubin group (all P>0.05). Conclusion: Moderate direct bilirubin level is associated with increased risk of all-cause death at 2 years after PCI compared with low level of direct bilirubin group.