Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli.

Transcription factor engineering has unique advantages in improving the performance of microbial cell factories due to the global regulation of gene transcription. Omics analyses and reverse engineering enable learning and subsequent incorporation of novel design strategies for further engineering. Here, we identify the role of the global regulator IhfA for overproduction of free fatty acids (FFAs) using CRISPRi-facilitated reverse engineering and cellular physiological characterization. From the differentially expressed genes in the ihfAL- strain, a total of 14 beneficial targets that enhance FFAs production by above 20 % are identified, which involve membrane function, oxidative stress, and others. For membrane-related genes, the engineered strains obtain lower cell surface hydrophobicity and increased average length of membrane lipid tails. For oxidative stress-related genes, the engineered strains present decreased reactive oxygen species (ROS) levels. These gene modulations enhance cellular robustness and save cellular resources, contributing to FFAs production. This study provides novel targets and strategies for engineering microbial cell factories with improved FFAs bioproduction.

Outcomes Associated with 50 mg/d and 100 mg/d Aspirin for the Prevention and Management of Cardiovascular Disease in Chinese Elderly: Single-Center Interim Analysis of a Multicenter, Prospective, Observational Study.

Purpose: Although aspirin can effectively reduce the occurrence of atherothrombosis, it is significantly associated with increased bleeding, with elderly individuals being at increased risk of cardiovascular diseases (CVD) and hemorrhage. This study aims to evaluate the efficacy and safety of aspirin 50 mg/d and 100 mg/d for the prevention and management of CVD in Chinese elderly. Patients and Methods: The Low-dose Aspirin for Primary and Secondary Prevention of Cardiovascular Disease in the Elderly Study (LAPIS) is a multicenter, prospective, observational cohort study, this study was a single-center interim analysis of LAPIS. Patients aged ≥60 and required long-term aspirin for primary and secondary prevention of CVD were eligible. From Apr 1, 2019 to Feb 28, 2022, 165 patients who received 50 mg/d aspirin and 261 patients who received 100 mg/d aspirin were included in the study. The incidence of major cardiovascular events (MACEs), bleeding events, and gastrointestinal adverse events were compared between two groups. Results: After adjusting for patient characteristics using propensity score matching, aspirin 100 mg/d was associated with increased incidence rates of total bleeding events (28.34 vs.17.25 events/100 patient-years, HR 1.671, 95% CI 1.024-2.712, P = 0.040) and minor bleeding events (27.63 vs.15.92 events/100 patient-years, HR 1.738, 95% CI 1.056-2.861, P = 0.031), whereas the incidence of MACE (6.35 vs 6.65 events/100 patient-years, HR 0.921, 95% CI 0.399-2.127, P = 0.848) and gastrointestinal adverse events (12.73 vs.10.42 events/100 patient-years, HR 1.206, 95% CI 0.623-2.337, P = 0.578) were similar between the two groups. Multivariate Cox analysis identified that aspirin dose (100 mg/d vs. 50 mg/d, HR 1.918, 95% CI 1.137-3.235, P = 0.015), concomitant use of other antiplatelets (HR 1.748, 95% CI 1.009-3.028, P = 0.046) and anticoagulants (HR 2.501, 95% CI 1.287-4.862, P = 0.007) were independently associated with bleeding events. Conclusion: 50 mg/d aspirin may be preferred to balance the safety and effectiveness in Chinese individuals over 60 years of age who need long-term aspirin for the prevention and management of CVD. Trial Registration: ChiCTR1900021980 (chictr.org.cn). Registered on 19 March 2019.

Genome Editing by CRISPR/Cas12 Recognizing AT-Rich PAMs in Shewanella oneidensis MR-1.

Homologous recombination-mediated genomic editing is urgently needed to obtain high-performance chassis of electroactive microorganisms. However, the existing tools cannot meet the requirement of genome-wide editing in Shewanella oneidensis. Here, we develop different CRISPR-Cas systems that are ideal to be employed in AT-rich sequences as the supplements to Cas9. AsCpf1 and BhCas12b show low cell toxicity and superior ability to target sequences and are thus screened out in S. oneidensis MR-1. The PAMs of AsCpf1 and BhCas12b are 5'-TTTV-3' and 5'-ATTN-3'. For gene deletion, ∼1-kb gene is knocked out and the editing efficiency is 41.67% by BhCas12b-mediated system. For gene replacement, endogenous promoter of nagK was substituted to a constitutive promoter with the efficiency of 25% through BhCas12b system. For gene insertion, the integration efficiency was up to 94.4% and 83.9% via CRISPR-BhCas12b and AsCpf1 tools. This study implies a great potential of CRISPR-BhCas12b/AsCpf1 systems recognizing AT-rich PAMs for genomic editing in S. oneidensis to facilitate multifaceted gene manipulation.

The role of Prostate Imaging Reporting and Data System score in Gleason 3 + 3 active surveillance candidates enrollment: a diagnostic meta-analysis.

BACKGROUND: The contemporary active surveillance (AS) criteria may result in an unsatisfactory misclassification rate, which may delay curative treatment for prostate cancer patients. The magnetic resonance imaging (MRI), not included in any AS criteria, provides useful information for prostate cancer diagnosis. Our goal is to evaluate the diagnostic performance of Prostate Imaging Reporting and Data Systems (PI-RADS) score, a standardized MRI reporting system, in AS candidates enrollment. METHODS: We searched Cochrane CENTRAL, PubMed, and Embase for pertinent studies through June 2018. The standard methods recommended for meta-analyses of diagnostic evaluation were employed. We draw the summary receiver operating characteristic (SROC) curve. Meta-regression analysis was performed to evaluate the effects of confounding factors. RESULTS: From the resulting 168 studies, 5 provided the diagnostic data on PI-RADS score and pathological results; 834 patients were included. All AS candidates in these studies were defined by Prostate Cancer Research International: Active Surveillance (PRIAS) criterion. The pooled estimates of PI-RADS 4 or 5 on adverse pathological features at radical prostatectomy (RP) among AS candidates were: sensitivity, 0.77 (95% confidence interval (CI), 0.71-0.82); specificity, 0.63 (95% CI, 0.55-0.71); positive predictive value, 0.72 (95% CI, 0.64-0.79); negative predictive value, 0.68 (95% CI, 0.63-0.73); and diagnostic odds ratio, 6 (95% CI, 4-8). The SROC curve was positioned toward the desired upper left corner of the curve, the area under the curve was 0.77 (95% CI, 0.73-0.80). The P-value for heterogeneity was <0.01. The pathological outcomes and endorectal coils contributed to the heterogeneity of sensitivity. The evidences supporting the advantage of PI-RADS v2 over v1 were not sufficient yet. CONCLUSION: AS candidates with PI-RADS 4 or 5 may be unsuitable for AS even though they fulfill current AS criteria. Those with PI-RADS 3 or less indicated relative safety for AS enrollment.

Contemporary Epstein Criteria with Biopsy-Naïve Multiparametric Magnetic Resonance Imaging to Prevent Incorrect Assignment to Active Surveillance in the PI-RADS Version 2.0 Era.

PURPOSE: The aim of this study is to evaluate the effectiveness of multiparametric magnetic resonance imaging (mp-MRI) in prostate cancer (PCa) patients with biopsy Gleason score ≤ 6 who may otherwise be assigned to active surveillance (AS). PATIENTS AND METHODS: This was a retrospective study of 90 patients who underwent transrectal systematic biopsy for prostate cancer with Gleason score ≤ 6 without neoadjuvant therapy, with radical prostatectomy (RP) conducted between September 2009 and March 2018. All patients underwent prebiopsy mp-MRI. The prostate imaging reporting and data system (PI-RADS) version 2.0 score was evaluated. The correlation between imaging results and pathological findings was analyzed. We established models based on Epstein criteria with or without PI-RADS score and evaluated their ability for screening of potential PCa AS candidates. RESULTS: Among 90 patients, 60 (66.7%) had upgrade (Gleason ≥ 7), 30 (33.3%) had extraprostatic extension, and 9 (10%) had seminal vesicle invasion on RP specimens. The rate of unfavorable disease was 67.8% (61 of 90). On multivariate analysis, independent risk factors for unfavorable disease were prostate-specific antigen density and PI-RADS score. The model based on Epstein criteria with PI-RADS score showed improved integrated discrimination improvement index and was superior to the classical Epstein criteria on decision curve analysis for screening potential prostate cancer AS candidates. CONCLUSIONS: Multiparametric MRI with PIRADS 2.0 provides useful supplementary information to Epstein criteria, and may prevent incorrect assignment to active surveillance.

Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells in upper tract urothelial carcinoma.

Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway has shown promising results in several malignancies. However, the prognostic significance of PD-L1 expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1 expression and its association with clinicopathological characteristics and oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor-infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients with UTUC. Associations of PD-L1 expression on tumor cells and TIMCs with clinicopathological characteristics and cancer-specific survival (CSS) were evaluated. Out of 162 patients, 20 (12.3%) and 35 (21.6%) had positive PD-L1 expression on tumor cells and TIMCs, respectively. Decreased E-cadherin expression was associated with PD-L1 positivity on tumor cells (P = 0.048) and PD-L1 negativity on TIMCs (P = 0.033). PD-L1 expression on tumor cells was higher in patients with preoperative chronic kidney disease (CKD) stage 4-5 than in those with no CKD or CKD stage 1-3 (P = 0.011). PD-L1 was differentially expressed in tumor cells and TIMCs in UTUC. Multivariate analyses revealed that PD-L1 expression on tumor cells independently predicted shorter CSS (P = 0.012), whereas PD-L1 expression on TIMCs independently predicted longer CSS (P = 0.034).

[Association between CMTM5 gene rs723840 single nucleotide polymorphism and high on asprin platelet reactivity].

OBJECTIVE: To elucidate the correlation between the single nucleotide polymorphism of CKLF-like MARVEL transmembrane member 5 (CMTM5) gene rs723840 and the occurrence of high on aspirin platelet reactivity (HAPR). METHODS: The present study is a case-control study. A total of 210 hospitalized patients in Peking University First Hospital were enrolled. Aspirin response was assessed by 0.5 g/L arachidonic acid (AA)-induced platelet aggregation ratio (PR), and ≥ 3/4 quartile of PR of the population was defined as HAPR. Accordingly all the enrolled 210 coronary artery diseases (CAD) patients were divided into HAPR group and No-HAPR group. The genotypes were determined by polymerase chain reaction (PCR) and sequencing analysis for rs723840 of CMTM5 gene. RESULTS: The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both HAPR group and No-HAPR group. Between the two groups, the genotypes frequencies in HAPR and No-HAPR groups were 48.4%, 51.6%, 0.0% and 73.7%, 22.9%, 0.034%, respectively (P=0.004). The C, T allele frequencies were significantly different in the two groups (P=0.031,OR=0.501, 95% CI: 0.264-0.947). CONCLUSION: Our study finds a significant correlation between CMTM5 gene rs723840 polymorphism and high on aspirin platelet reactivity.

[Correlation between the level of the urinary 11-dehydrothromboxane B2 and the clinical efficacy of aspirin in patients with type 2 diabetes and coronary artery disease].

OBJECTIVE: To elucidate the correlation between urinary 11-dehydro-thromboxane B2 (11dhTxB2) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease (CAD). METHODS: In this prospective cohort study, 169 aged patients with type 2 diabete accompanying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detected using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group. RESULTS: Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was (3 687±3 052) ng/g, while the urinary 11dhTxB2 was (1 954±859) ng/g in patients after 100 mg/d aspirin treatment (P<0.001). Prevalence of HAPR in patients with type 2 diabete accompanying CAD were 32.5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group (P<0.05). CONCLUSION: Urinary 11dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD.

Comparison between urinary 11-dehydrothromboxane B2 detection and platelet Light Transmission Aggregometry (LTA) assays for evaluating aspirin response in elderly patients with coronary artery disease.

Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. The aim of our study was to compare between two established methods of aspirin response, urinary 11-dehydrothromboxane B2 (11dhTXB2) and platelet Light Transmission Aggregometry (LTA) assays in elderly Chinese patients with coronary artery disease (CAD), and to investigate the clinical significance of both methods in predicting cardiovascular events. Urinary 11dhTxB2 assay and arachidonic acid-induced (AA, 0.5mg/ml) platelet aggregation by Light Transmission Aggregometry (LTAAA) assay were measured to evaluate aspirin responses. High-on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1500pg/mg or AA-induced platelet aggregation≥15.22%-the upper quartile of our enrolled population. The two tests showed a poor correlation for aspirin inhibition (r=0.063) and a poor agreement in classifying HAPR (kappa=0.053). With a mean follow-up time of 12months, cardiovascular events occurred more frequently in HAPR patients who were diagnosed by LTA assay as compared with no-HAPR patients (22.5% versus 10.6%, P=0.039, OR=2.45, 95% CI=1.06-5.63). However, the HAPR status, as determined by urinary 11dTXB2 measurement, did not show a significant correlation with outcomes.

Antithrombotic therapy in elderly patients with non-valvular atrial fibrillation: a pilot study.

OBJECTIVE: Non-valvular atrial fibrillation (NVAF) is one common arrhythmia in the elderly. However, use of antithrombotic therapy in this population is not well known in the People's Republic of China. This study aimed at investigating antithrombotic therapy status in elderly patients with NVAF in our hospital. METHODS: A cross-sectional study of consecutive geriatric patients aged ≥60 years with NVAF who discharged from our hospital between January 2012 and December 2013 were collected. CHA2DS2-VASc score (cardiac failure or dysfunction, hypertension, age ≥75 [doubled], diabetes, stroke or transient ischemic attack [doubled], vascular disease, age 65-74, and sex category [female]) was used to analyze antithrombotic indication. RESULTS: We consecutively collected data of 1,000 discharged elderly patients (≥60 years) with NVAF (mean age 75.3±8.0 years, 75 years or older 54.7%, female 42.7%). The proportion of paroxysmal atrial fibrillation and non-paroxysmal atrial fibrillation (persistent or permanent) patients were 39.4% and 60.6%, respectively. Among 1,000 patients, 29.1% received oral anticoagulant therapy (OAT), including warfarin (27.8%) and novel oral anticoagulants (1.3%), 39.5% of patients received antiplatelet therapy, and 31.4% received neither therapy. Based on CHA2DS2-VASc score for stroke risk stratification, 68.9% patients with score ≥1 and 70.2% patients with score ≥2 received antithrombotic therapy, while the rates of OAT were 29.1% and 29.5%, respectively. Among patients with high stroke risk, those with paroxysmal atrial fibrillation were less likely to receive OAT compared with the patients with non-paroxysmal atrial fibrillation (19.5% vs 35.7%, P<0.001). The patients ≥75 years old had lower rate of OAT than the patients <75 years old (25.8% vs 34.8%, P=0.003). The patients with coronary artery disease had lower rate of OAT than the patients without coronary artery disease (24.4% vs 33.4%, P=0.003). Sex and history of stroke or transient ischemic attack had no effect on the use of OAT (30.8% vs 27.9%, P=0.326 and 28.8% vs 29.8%, P=0.761, respectively). CONCLUSION: OAT in elderly patients with NVAF in our hospital is underused, especially in those patients with higher risk of stroke.

[Comparison between CHADS2 score and CHA2DS2-VASc score on assessing the risk of ischemic stroke in patients with nonvalvular atrial fibrillation].

OBJECTIVE: To compare the value between CHADS2 score and CHA2DS2-VASc score on assessing the risk of ischemic stroke in patients with nonvalvular atrial fibrillation. METHODS: In this retrospective study, nonvalvular atrial fibrillation patients with acute ischemic stroke hospitalized from January 2004 to March 2013 in our department were included. CHADS2 score (range, 0-6) and CHA2DS2-VASc score (range, 0-9) before acute ischemic stroke was calculated. For both schemes, patients were also classified with scores of 0, 1 and ≥ 2 in low-risk, intermediated-risk and high-risk categories, respectively, the difference between the two risk stratification schemes was evaluated by each category. RESULTS: A total of 599 patients [320 men, mean age (75.4 ± 9.1) years] were collected. According to CHADS2 score, 30 (5.0%), 132 (22.0%) and 437 (73.0%) patients were classified in the low-risk, intermediated-risk and high-risk categories, respectively. The corresponding classification by CHA2DS2-VASc score was 6(1.0%), 25(4.2%) and 568 (94.8%) cases. The number of low-risk category patients (5.0% vs. 1.0%, χ(2) = 22.04, P < 0.001) and in intermediate-risk category patients (22.0% vs. 4.2%, χ(2) = 84.81, P < 0.001, Kappa = 0.075) was significantly higher in CHADS2 score group than in CHA2DS2-VASc score group, and the consistence between the two scores was poor (Kappa = 0.322). There were less patients classified in the high-risk group by CHADS2 score compared to CHA2DS2-VASc score (73.0% vs. 94.8%,χ(2) = 131.00, P < 0.001, Kappa = 0.257). CONCLUSION: Compared with CHADS2 score, CHA2DS2-VASc score is more valuable in predicting ischemic stroke for patients with nonvalvular atrial fibrillation.

[Impact on the carotid intima-medial thickness and safety of rosuvastatin in Chinese patients with carotid atherosclerosis: a meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of rosuvastatin in Chinese patients with carotid atherosclerosis. METHOD: A systematic search of Pubmed, EMBase, CENTRAL, CBMdisc, CNKI and WANFANG databases up to January 2013 was performed to identify studies comparing rosuvastatin with a placebo or other statins on carotid intima-medial thickness (IMT) with a minimum follow-up of 6 months in Chinese patients. Meta-analysis was performed by using RevMan 5.0 software after the strict evaluation of the methodological quality of the included studies independently by two reviewers. RESULTS: Twenty-eight studies involving 1 392 individuals were included in this review. The pooled weighted mean difference (WMD) between rosuvastatin and placebo or control on IMT was 0.28 mm (95%CI 0.14-0.42, P < 0.01), with 0.31 mm (95%CI 0.14-0.49, P < 0.01) on 6-8 months and 0.16 mm (95%CI 0.05-0.27, P = 0.005) on 12 months, respectively. Analysis on studies in core journals showed the WMD between rosuvastatin and placebo or control on IMT was 0.18 mm (95%CI 0.09-0.27, P < 0.01). The WMD between rosuvastatin and other statins on IMT was 0.06 mm (95%CI 0.04-0.08, P < 0.01). The WMD between rosuvastatin and placebo or control on plaque score was 0.89 (95%CI 0.78-0.99, P < 0.01). The WMD between rosuvastatin and placebo or control on plaque area was 1.46 (95%CI 0.67-2.25, P < 0.01).Reports of adverse effect were elevated liver enzyme (2.30%, 19/825), elevated muscle enzyme (0.73%, 6/825), muscle aches (0.61%, 5/825). CONCLUSIONS: Rosuvastatin therapy is effective and safe to decrease IMT in Chinese patients with carotid atherosclerosis.

[The clinical features of gastrointestinal bleeding complicating aortic stenosis].

OBJECTIVE: To deepen the understanding about Heyde's syndrome by investigating the clinical characteristics and prognosis of the patients with aortic valve stenosis complicating with gastrointestinal bleeding. METHODS: Patients with aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our hospital from 2001 to 2011 were retrieved and analyzed. RESULTS: In all the 443 157 in-patients, 474 patients were diagnosed with aortic valve stenosis (0.11%, 474/443 157) and 14 patients (9 males and 5 females, aged 53-87 years old) with gastrointestinal bleeding coincidently(2.95%, 14/474). Among the 14 patients, 3 were moderate aortic valve stenosis, 11 severe aortic valve stenosis. The aortic valve peak flow velocity was 324-709 (480.54 ± 188.25) cm/s and the mean aortic valve pressure gradient was 21.04-91.56 (56.93 ± 29.90) mm Hg(1 mm Hg = 0.133 kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1 of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC) count were significantly lower than the normal range [(69 ± 28) g/L and (2.71 ± 2.04)×10(12)/L, P < 0.05]. Their mean corpuscular volume(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet(PLT) count, prothrombin time (PT) and international normalized ratio (INR) were in normal range [(90.21 ± 2.94) fl, (29.39 ± 1.99) pg, (327.57 ± 14.82) g/L, (185.13 ± 22.55)×10(9)/L, (11.4 ± 1.04) s and 1.22 ± 0.44, respectively]. Among all the 14 patients, 13 were over 65 years old and they all accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was found in 6 patients with 4 lesions located in descending colon and 2 located in sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer, and another of duodenal ulcer, while no definite hemorrhage foci were found in the other 11 patients. A total of 6 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent gastrointestinal bleeding was ever found. Conservative treatment was performed in the other 5 patients with severe aortic valve stenosis (5/11) and resulted in sudden death in 2 patients (2/5). CONCLUSIONS: Prompt echocardiography and gastrointestinal endoscopy should be performed in the elderly patients with obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment of Heyde's syndrome. AVR is a fundamental procedure to improve the prognosis of Heyde's syndrome.

Shenyuan, an extract of American Ginseng and Corydalis Tuber formula, attenuates cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and oxidative stress in a porcine model of acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis. MATERIALS AND METHODS: A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg·d, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kg·d, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kg·d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg·d, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI. RESULTS: Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P < 0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C. CONCLUSION: Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI.

[Aspirin response and related factors in aged patients].

OBJECTIVE: To explore clinical and laboratory factors associated aspirin response, and the association between gastrointestinal bleeding and aspirin response in aged patients. METHODS: A total of 136 patients aged 60 and over [mean age (74.9 ± 7.0) years] with ischemic heart disease and at high risk for ischemic heart disease were included. Arachidonic acid induced platelet aggregation (AA-Ag) was measured before and at 7(th) day after taking aspirin (100 mg/d). Patients were followed for 6 months and incidence of gastrointestinal bleeding was obtained. RESULTS: Post-treatment AA-Ag was significantly reduced compared to baseline (13.29% ± 5.52% vs. 73.20% ± 7.32%, P < 0.05). A heterogeneous distributed post-treatment AA-Ag was observed (range 0.42% to 30.50%). Post-treatment AA-Ag was positively correlated with baseline AA-Ag (r = 0.493, P < 0.01). The level of post-treatment AA-Ag was significantly higher in the fourth quartile group at baseline than in the others quartile groups at baseline. Patients aged 80 years and over had significantly lower post-treatment AA-Ag (10.25% ± 4.68%) compared with patients of 60 - 69 years (13.96% ± 5.20%) and of 70 - 79 years (13.73% ± 5.48%, all P < 0.01). The incidence of patients in the lowest quartile of post-treatment AA-Ag was significantly higher in patients ≥ 80 years (38.24%) than in patients of 60 - 69 years (11.1%) and of 70 - 79 years (24.0%). Multiple variable analysis revealed post-treatment AA-Ag was significantly influenced by baseline AA-Ag, ≥ 80 years old, diabetes mellitus and acute coronary syndrome. We observed 4 (2.9%) mild gastrointestinal bleeding during follow up. Post-treatment AA-Ag was in the lowest quartile in 3 patients with mild gastrointestinal bleeding. CONCLUSIONS: Increased baseline platelet reactivity as well as diabetes mellitus and acute coronary syndrome are associated with low aspirin response in the aged patients. Aspirin response is significantly higher in very old patients.

[Effects of in vivo transfer of human chemokine-like factor 1 gene on cardiac function after acute myocardial infarction in rats].

OBJECTIVE: To study the effects of chemokine-like factor 1(CKLF1)-plasmid transfer on cardiac function in a rat acute myocardial infarction (AMI) model. METHODS: Thirty male SD rats were randomly devided into 3 groups. One hundred micrograms of CKLF1-plasmid, empty plasmid or saline were injected intramuscularly with in vivo electroporation, respectively. Rats were subjected to left coronary artery ligation on the 6th day after gene transfer. Ultrasonic cardiography and hemodynamics were conducted and evaluated on the 22nd day after gene transfer. Then, the animals were sacrificed for determination of percentage of myocardial infarcion. RESULTS: The left ventricular ejection fraction in CKLF1 group (67.02% +/- 12.24%) was significantly higher than that in the saline group (43.64% +/- 7.82%) and empty plasmid group (47.56% +/- 4.10%), P<0.05. Fractional shortening of left ventricle in CKLF1 group (33.83% +/- 10.15%) was higher than that in saline group (18.49% +/- 3.96%) and empty plasmid group (20.85% +/- 2.24%), P<0.05. The maximal velocity of left ventricular pressure ascensus was higher in CKLF1 group [(5 720.01 +/- 826.32) mmHg/s, 1 mmHg=0.133 kPa] than in saline group [(3 955.69 +/- 685.91) mmHg/s] and in empty plasmid group [(4 412.03 +/- 500.74) mmHg/s)], P<0.05. And the maximal velosity of left ventricular pressure descensus was higher in CKLF1 group [(4 636.23 +/- 407.17) mmHg/s] than in saline group [(2 984.82 +/- 615.24) mmHg/s] and in empty plasmid group [(2 963.87 +/- 419.36) mmHg/s], P<0.05. While the percentage of myocardial infarction in CKLF1 group (29.63% +/- 3.93%) was smaller than that in saline group (38.01% +/- 5.48%) and in empty plasmid group (37.50% +/- 6.33%), P<0.05. CONCLUSION: CKLF1 gene transfer can limit the mass of myocardial infarction and improve post-infarction cardiac function.

[The predictive value of Holter recordings to detect moderate-severe obstructive sleep apnea syndrome].

OBJECTIVE: To evaluate the predictive value of Holter ECG recordings for patients with moderate-severe obstructive sleep apnea and hypopnea syndrome (OSAHS). METHODS: Holter recordings was performed in 76 patients who were diagnosed OSAHS by polysomnography (PSG) within one month from Jan. 2008 to July 2009 in our hospital. Twenty-eight patients were identified as mild OSAHS (AHI < or = 20) and forty-eight patients were moderate-to-severe OSAHS (AHI > 20). The indexes of heart rate variability (HRV), total scores of thirteen sleep apnea risk indexes of Holter recordings and BMI were analyzed by bivariate Logistic regression analysis. RESULTS: Clinical features (eg. Gender, age, complicated with hypertension, coronary heart disease, diabetes mellitus, hyperglycemia, and taken beta-blocker), total scores, the sum of thirteen sleep apnea risk scores collected by Holter recordings (5.64 + or - 2.33 vs. 6.42 + or - 2.22, respectively, P > 0.05) were similar between patients with mild OSAHS and moderate-to-severity OSAHS. VLF/Total Power > 70%, the difference of daytime/nighttime LF Power < -70 and BMI were independent predictors of moderate-to-severe OSAHS with OR 3.98 (1.087 - 14.596), 3.69 (1.106 - 12.285) and 1.28 (1.062 - 1.544), respectively (all P < 0.05). CONCLUSIONS: VLF/Total Power and the difference of daytime/nighttime LF Power and BMI could be used as screening parameters to recognize patients with moderate-to-severe OSAHS.

[In vivo transfer of human chemokine-like factor 1 gene increases peripheral blood CD34+ stem cells after myocardial infarction in rats].

OBJECTIVE: To assess the influence of different doses of CKLF1 plasmid on the dynamics and magnitude of the mobilization of the mobilization bone of marrow stem cells in a rat AMI model. METHODS: Different doses of plasmid DNA encoding CKLF1 gene, empty plasmid or saline were injected into male SD rats intramuscularly with in vivo electroporation. Rats were subjected to left coronary artery ligation 6 days after gene transfer. Peripheral blood samples were drawn and CD34+ cells were assayed by FACS calibur flow-cytometer. The changes in absolute number of CD34+ cells were evaluated. RESULTS: Expressions of CKLF1 mRNA and protein were detected in the injection site 7 days after gene transfer. Five days after gene transfer, the CD34+ cells numbers in CKLF1 groups were significantly higher than those in empty plasmid group, especially in CKLF1 100 microg group (16.63x10(6)/L vs 4.98x10(6)/L, P<0.01). On the 5-7 days, the CD34+ cell numbers in CKLF1 groups reached the peak and the peak number was 3.88 times that of baseline in CKLF1 100 microg group (P<0.01). After AMI, the cell numbers of 1 day to 7 days were significantly higher than those of the baseline in empty plasmid group and saline group. In comparison to empty plasmid group, CKLF1 groups were associated with still higher numbers of cells 1 day after AMI (P< 0.05), especially in CKLF1 100 microg group (14.61x10(6)/L vs 7.85x10(6)/L, P<0.01). CONCLUSION: CKLF1 gene transfer significantly increases the mobilization of CD34+ stem cells in acute myocardial infarction rats.