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Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated.Therapeutic drug monitoring data were collected from 151 paediatric patients aged 10 to 17 years who received olanzapine. The model was developed with a NONMEM software program. The final model validation and evaluation were assessed by bootstrap, diagnostic scatter plots, and normalized prediction distribution error (NPDE). Regimens of different dosages were simulated to reach the target concentration levels of 20 ng/ml, by using the final model with typical parameters.The one-compartment model was considered the best fit for the data. Typical estimates of the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) in the final model were 0.142 hOur results identified concomitant valproate and sex as significant covariates in olanzapine population pharmacokinetics. Our model may be a useful tool for recommending dosage adjustments for physicians. The pharmacokinetics of olanzapine in patients aged 10 to 17 years was generally similar to that of adults and the elderly.

Background Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status. Methods A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs. Results During a median of 5.1 (interquartile range 3.9 to 5.9) years’ follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149–2.955), 1.828 (1.165–2.867), 2.212 (1.396–3.507), all p Conclusions In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.

Background Coronary artery ectasia (CAE) is an angiographic finding of abnormal coronary dilatation. Inflammation plays a major role in all phases of atherosclerosis. We investigated the relationship between CAE and serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels to test our hypothesis that patient age is associated with the efficacy of anti-inflammatory therapy for CAE. Methods We conducted a prospective analysis of 217 patients with CAE treated at the Department of Cardiology, Shanghai East Hospital, Ji’an Campus and the Baoshan People’s Hospital, from January 1, 2015 to July 30, 2019. Baseline data of patients, including sex; age; and history of hypertension, hyperlipidemia, and diabetes, were collected from patient medical records. Study participants were grouped by age as follows: CAE-A (n = 60, age ≤ 50 years), CAE-B (n = 83, 50 years n = 74, age > 70). Additionally, there was a control (NC) group (n = 73) with normal coronary arteries. Results All patients received oral rosuvastatin therapy (10 mg, QN quaque nocte) when they were diagnosed with CAE and maintained good follow-up, with a loss rate of 0.0% at the end of the 6-month follow-up. The NC group received regular symptom-relieving treatments and rosuvastatin therapy. Of these four groups, the inflammatory markers, hs-CRP and IL-6, were significantly higher in patients with CAE than in the NCs (p P = 0.048, P = 0.025). Logistic regression analysis showed that hs-CRP (OR = 1.782, 95% CI: 1.124–2.014, P = 0.021) and IL-6 (OR = 1.584, 95% CI: 1.112–1.986, P = 0.030) were independent predictors of CAE. The inflammatory markers were higher in the CAE-A group than in the CAE-B group and higher in the CAE-B group than in the CAE-C group. Follow-up after 6 months of rosuvastatin therapy showed a significantly greater reduction in hs-CRP and IL-6 levels in the CAE-A group than in the CAE-B group, which again were greater in the CAE-B group than in the CAE-C group. Conclusions Anti-inflammatory therapy using rosuvastatin was more effective in younger CAE patients, indicating the need for early statin therapy in CAE.

Background The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status. Methods Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p Conclusions In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.

Background Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM. Methods A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated. Results A total of 464 MACEs were documented. Both Kaplan–Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24–2.70, p Conclusions The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD, suggesting that sdLDL may be useful for CAD risk stratification in DM.

Familial hypercholesterolemia (FH) is one of the most common causes of premature myocardial infarction (MI). However, The patterns of FH remained unrecognized in clinical care, especially in very young patients (VYPs, ≤35 years) with MI. The present study enrolled a total of 1,093 VYPs (≤35 years) presenting a first MI. Clinical diagnosis of FH was made using Dutch Lipid Clinic Network criteria. Coronary severity was assessed by Gensini score (GS). Patients were followed for a median of 40-months with cardiac death, stroke, MI, post-discharge revascularization or unstable angina as primary endpoints. The detected rates of definite/probable FH were 6.5%. The prevalence reached up to 10.3% in patients ≤25 years. The FH had similar levels of comorbidities but was younger, more likely to be very high risk (VHR) and had higher GS (p

Background Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. Methods and results A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan–Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group ( n =189) and non-events group ( n =2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099–2.496, p =0.016). Additionally, the Kaplan–Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival ( p =0.016). Conclusions The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings.

Our study explored the effects of SOST gene silencing on the proliferation, apoptosis, invasion, and migration of human osteosarcoma cells through Wnt/β-catenin signaling pathway. Fresh tissues were obtained from 108 patients with osteosarcoma and 46 patients with osteochondroma. Human osteosarcoma cells (MG-63, U2-OS, HOS, and Saos-2) and normal osteoblast (hFoB1.19) were selected and cultured. Osteosarcoma cells were grouped randomly into the blank group, the scrambled control group, and the SOST-siRNA group. Cell proliferation was determined by MTT assay. Cell cycle and apoptosis were tested by flow cytometry. Transwell and scratch test were performed to determine cell invasion and migration. The qRT-PCR and Western blotting were used to detect mRNA and protein expression level of sclerostin, Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7. The activity of caspase-3 was assessed by immunocytochemistry. Alkaline phosphatase (ALP) activity was measured using P-nitrophenylphosphate as a substrate. Low SOST mRNA and sclerostin protein expression levels were observed in osteosarcoma tissues and cells. Compared with the blank and scrambled control groups, sclerostin expression, apoptotic cells, ALP activity, and caspase-3 activity were down-regulated, while the proliferation, invasion, and migration abilities of osteosarcoma cells were evidently enhanced in the SOST-siRNA group. After SOST gene silencing, the mRNA and protein expression levels of Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7 in osteosarcoma cells and β-catenin protein expression levels in the nucleus and cytoplasm were significantly elevated. SOST gene silencing promotes the proliferation, invasion, and migration, and inhibits apoptosis of osteosarcoma cells by activating Wnt/β-catenin signaling pathway.

Recent guidelines recommended both low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are the primary target of lipid modulating therapy. However, which lipid measure is most closely related to the severity of coronary atherosclerosis has not yet been assessed.We studied 1757 consecutive subjects undergoing coronary angiography who were not receiving any lipid-lowering therapy. Low-density lipoprotein cholesterol was measured directly, and non-HDL-C was calculated. The severity of coronary stenosis was determined using the Gensini Score (GS) system.In the overall population, LDL-C and non-HDL-C were all dramatically increased according to the quartiles of GS (p0.001, both). In patients with coronary atherosclerosis (n=1097), non-HDL-C (r=0.138, p0.001) was more closely related to GS than LDL-C (r=0.113, p0.001) tested by Spearman correlation analysis. Multivariate logistic regression analysis suggested that non-HDL-C (OR=1.326, 95% CI 1.165-1.508, p0.001) was slightly superior to LDL-C (OR=1.286, 95% CI 1.130-1.463, p0.001) in predicting high GS after adjusting for potential confounders. Among patients with LDL-C less than the median, discordant non-HDL-C could not provide extra value in predicting high GS (OR=0.759, 95% CI 0.480-1.201). However, among patients with LDL-C greater than or equal to the median, the cardiovascular risk was overestimated for patients with discordant non-HDL-C (OR=0.458, 95% CI 0.285-0.736).Our data support the use of non-HDL-C ahead of LDL-C in predicting the severity of coronary atherosclerosis, especially among patients with LDL-C greater than or equal to the median.

It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C), but its impact on lipoprotein subfractions and oxidized low-density lipoprotein (oxLDL) has not been determined. The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein (HDL) as well as oxLDL in untreated patients with coronary atherosclerosis (AS). Thirty-six subjects were enrolled in this study. Of them, 18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls. The plasma lipid profile, lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively. The results showed that pitavastatin treatment indeed not only decreased LDL-C, total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB) levels, and increased HDL cholesterol (HDL-C), but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions. Meanwhile, pitavastatin could decrease plasma oxLDL levels. Furthermore, a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment. We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.

Aim: DCK is a rate-limiting enzyme in cytarabine activation. rs4643786 and rs67437265 (P122S) variants are reported to affect DCK activity. Patients & methods: A total of 282 newly diagnosed acute myeloid leukemia (AML) patients were treated with cytarabine combined chemotherapy and genotyped for rs4643786 and rs67437265. Prognosis data were obtained through regular follow-up. DCK mRNA expression was detected in pretreatment blood or bone marrow mononuclear cells. Results: rs4643786 showed strong linkage disequilibrium with rs67437265. rs4643786 CT heterozygotes showed significantly higher complete remission rate (p = 0.028), superior overall survival (p = 0.006) and relapse-free survival (p = 0.020) than wild-type TT homozygotes. rs4643786 polymorphism was an independent predictor for AML prognosis. Conclusion: DCK rs4643786 may serve as an independent predictor of drug response and AML outcome.

// Xiao-Qing Yuan 1, 2 , Dao-Yu Zhang 1, 2 , Han Yan 1, 2 , Yong-Long Yang 3 , Ke-Wei Zhu 1, 2 , Yan-Hong Chen 1, 2 , Xi Li 1, 2 , Ji-Ye Yin 1, 2 , Xiao-Lin Li 4 , Hui Zeng 4 , Xiao-Ping Chen 1, 2, 5 1 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2 Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China 3 Department of Pharmacy, Haikou People’s Hospital and Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou 570311, P. R. China 4 Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 5 Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, P. R. China Correspondence to: Xiao-Ping Chen, email: chenxp74@hotmail.com Hui Zeng, email: androps2011@hotmail.com Keywords: DNMT3A, polymorphism, AML, chemosensitivity, prognosis Received: January 15, 2016 Accepted: July 26, 2016 Published: August 09, 2016 ABSTRACT DNMT3A mutation is known as a recurrent event in acute myelogenous leukemia (AML) patients. However, association between DNMT3A genetic polymorphisms and AML patients’ outcomes is unknown. DNMT3A 11 SNPs (rs11695471, rs2289195, rs734693, rs2276598, rs1465825, rs7590760, rs13401241, rs7581217, rs749131, rs41284843 and rs7560488) were genotyped in 344 diagnostic non-FAB-M3 AML patients from southern China. Patients underwent combined chemotherapy with cytarabine and anthracyclines. DNMT3A mRNA expression was analyzed in PBMCs from randomly selected AML patients. Multivariate analysis and combined genotype analysis showed that rs2276598 was associated with increased while rs11695471 and rs734693 were associated with decreased chemosensitivity ( P

Coronary collateral circulation (CCC) plays an important role in protecting myocardium from ischemic damage. The studies on factors which impact on CCC might be of great clinical interest. The aim of the present study was to evaluate endothelin-1 (ET-1) as a potential predictor for poor or good CCC in patients with angiography-proven ≥95% coronary occlusion.We screened 1038 consecutive patients with ≥95% occlusion in at least one major epicardial coronary artery detected by coronary angiography. Of these, 663 patients were classified into the poor CCC group with Rentrop 0-2 grade collateral circulation and 375 patients into the good CCC group with Rentrop 3 grade. The association of plasma ET-1 levels with collateral status was assessed.We found that patients in the poor CCC group had a higher ET-1 level than those in the good CCC group (0.59±0.48 vs. 0.39±0.32pmol/L, p0.001), and the ET-1 values increased with the descent of the Rentrop grades (p for trend0.001). Moreover, multivariate logistic regression analysis revealed an independent association between ET-1 and collateral status (odds ratio [95% CI] for poor CCC 2.27 [1.60-3.22], p0.001). Additionally, the association presented significance in both men (odds ratio [95% CI] for poor CCC 3.18 [2.20-4.74], p0.001) and women (odds ratio [95% CI] for poor CCC 3.10 [1.36-7.85], p=0.011) when the sex-specific analysis was performed.Plasma ET-1 level may be a useful, easily available marker for predicting the degree of CCC in patients with ≥95% coronary chronic occlusion.

Patients with advanced epithelial ovarian cancer often experience disease recurrence after standard therapies, a critical factor in determining their five-year survival rate. Recent reports indicated that long-term or short-term survival is associated with varied gene expression of cancer cells. Thus, identification of novel prognostic biomarkers should be considered. Since the mouse genome is similar to the human genome, we explored potential prognostic biomarkers using two groups of mouse ovarian cancer cell lines (group 1: IG-10, IG-10pw, and IG-10pw/agar; group 2: IG-10 clones 2, 3, and 11) which display highly and moderately aggressive phenotypes in vivo. Mice injected with these cell lines have different survival time and rates, capacities of tumor, and ascites formations, reflecting different prognostic potentials. Using an Affymetrix Mouse Genome 430 2.0 Array, a total of 181 genes were differentially expressed (P

To investigate the association between serum C-reactive protein (CRP) levels and coronary collateral circulation (CCC) in Chinese patients with angiography-proven ≥95% coronary stenosis.In this study, 1158 patients with angiography-proven ≥95% occlusion in ≥1 major epicardial coronary artery were enrolled, and then classified into two groups: poor CCC (Rentrop grades 0-1) and good CCC (Rentrop grades 2-3). CRP levels were grouped using the following two models: Model 1 discretized CRP group with 33.33% and 66.66% as the critical values and Model 2 with 1.0 and 3.0 mg/L as the cut off values.There were significant differences in serum CRP levels between the two groups (5.76 ± 3.45 vs. 3.49 ± 2.44 mg/L, respectively; p 0.001), and compared with the first CRP tertile, the risks of poor CCC were higher in the second and third CRP tertiles (OR 2.31, 95%CI [1.67-3.19], OR 6.25, 95%CI [4.52-8.62], respectively). The receiver operating characteristic curve analysis indicated that the optimal cutoff value of CRP to predict poor CCC was 4.21 mg/L with 59.6% sensitivity and 74.33% specificity.CRP levels are an independent predictor for poor CCC and might supply a useful biomarker in clinical applications. Key messages C-reactive protein (CRP) is a non-specific inflammatory marker that is regarded as an independent risk and prognostic factor for individuals who suffer from coronary artery disease (CAD) and cardiovascular disorders. In a Chinese cohort of patients with coronary artery occlusion or stenosis of ≥95% TIMI grade 1 anterograde-flow, the relationship between CRP concentrations and angiographically visible coronary collateral (CC) was assessed. Our data indicated that elevated CRP associated with a significant impairment in CC development, and might supply a useful biomarker in clinical applications.

Background: Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats. Methods: Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis. Results: Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks. Conclusions: Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling.

Background: The currently available polysomnography (PSG) equipments and operating personnel are facing increasing pressure, such situation may result in the problem that a large number of obstructive sleep apnea (OSA) patients cannot receive timely diagnosis and treatment, we sought to develop a nomogram quantifying the risk of OSA for a better decision of using PSG, based on the clinical syndromes and the demographic and anthropometric characteristics. Methods: The nomogram was constructed through an ordinal logistic regression procedure. Predictive accuracy and performance characteristics were assessed with the area under the curve (AUC) of the receiver operating characteristics and calibration plots, respectively. Decision curve analyses were applied to assess the net benefit of the nomogram. Results: Among the 401 patients, 73 (18.2%) were diagnosed and grouped as the none OSA (apnea-hypopnea index [AHI]

Few studies had examined the role of ABO blood groups on CAD in hypertensive patients with different blood pressure (BP) controls.A total of 2708 patients with primary hypertension (HTN) were consecutively enrolled and underwent coronary angiography (CAG) due to angina-like chest pain. The severity of coronary artery stenosis was assessed by Gensini score (GS). Patients were divided into two groups due to results of CAG: HTN with CAD (n = 2185) and HTN without CAD (n = 523). Poor BP control was defined as systolic BP (SBP) ≥ mean in the study. Multivariable regression analysis was used to determine the potential impact of ABO blood groups on risk of the presence and severity of CAD.Compared to HTN without CAD group, the percentage of A blood group was statistically higher and O blood group was significantly lower in HTN with CAD group. Moreover, percentage of the angiography-proven CAD was higher in A blood group than that in non-A blood group (p0.05). After adjusting for confounding factors, A blood group was independently associated with CAD (odds ratio (OR): 1.422; 95% confidence interval (CI): 1.017-1.987; p = 0.039) and GS (β = 0.055, p = 0.046) in patients with poor BP control.A blood group was an independent risk factor for the presence and severity of CAD in hypertensive patients with poor BP control.

Although previous studies have demonstrated the relationship between ABO blood groups and cardiovascular disease, the association of ABO blood type with spontaneous recanalization (SR) in patients with acute myocardial infarction (AMI) has not been previously investigated.We performed an initial exploratory study on the association of ABO blood groups with the presence of SR in 1209 patients with AMI. They were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) grades: no-SR group (TIMI 0-1, n = 442) and SR group (TIMI 2-3, n = 767). To confirm our primary findings, data from a second AMI population (n = 200) was analyzed.In the initial data, SR group had a significantly higher percentage of blood type O and a lower percentage of blood type A compared to the no-SR group. Multivariate logistic regression analysis showed that blood type O was positively associated with SR (odds ratio: 1.40, 95% confidence interval: 1.05-1.87, p = .02), and this finding was confirmed in our second population.The present study demonstrates that blood type O was independently and positively associated with an open culprit artery in patients with AMI, suggesting that the ABO blood type is not only associated with the susceptibility to coronary artery disease but also to spontaneous reperfusion in AMI patients.

Background Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to be related to several risk factors and diseases such as inflammatory markers and coronary artery disease. The aim of present study was to investigate whether plasma PCSK9 concentration was associated with coronary artery calcification. Methods A total of 403 consecutive untreated patients with angina-like chest pain, who received electron beam computed tomography, were enrolled and a coronary artery calcification score (CACS) was also measured. The baseline clinical characteristics were collected and blood sample was taken after 12-h fasting. The plasma PCSK9 concentrations were determined by ELISA in all patients, and the relationship between plasma PCSK9 concentrations and CACS was investigated. Results Patients with coronary artery calcification (CACS > 0) had significant higher plasma PCSK9 concentrations compared with those (CACS = 0) without coronary artery calcification (258.58 ± 69.53 ng/mL vs. 202.53 ± 52.17 ng/mL, P Conclusion A positive association between plasma PCSK9 concentration and coronary artery calcification in untreated patients with angina-like chest pain was observed in our study, suggesting that further investigation may be needed in order to confirm our primary findings and explore the clinical implications.

With the increasing longevity and the growing size of the aging population, China is among the developing countries with the greatest burden of osteoporotic fractures (OFs). Identification of individuals at high fracture risk to provide early treatment in developing countries with limited resources remains a challenge. Our aim was to calculate the FRAX® values in a selected mainland Chinese population the day before the occurrence of an OF and to compare the results with the Osteoporosis Foundation (NOF) thresholds. To define a population at high fracture risk, we selected patients in the orthopedic emergency cohort from Shanghai Sixth People's Hospital, China. To calculate the FRAX® the day before the actual OF, the actual fracture was not considered as a previous fracture. Subjects with a FRAX® value lower than the NOF thresholds were not considered at high risk. One-hundred ninety-eight patients were included with a mean age of 69.9 ± 10.1 years old, and 78.8 % were female. Major fracture sites included hip (41.9 %), proximal humerus (22.2 %), forearm (27.8 %), spine (6.6 %), and pelvis (1.5 %). Overall, only two (1.0 %) patients had a 10-year major fracture probability ≥20 %, and 84 (42.4 %) patients had a 10-year hip fracture probability ≥3 %. More than half of the population was not identified to be at high risk by the FRAX® BMI (body mass index). For age groups 55-59, 60-69, 70-79, and 80-90 years old, respectively, the mean FRAX® BMI values (major OF/hip fracture) were 3.5/0.7, 5.7/1.8, 8.2/4.7, and 8.6/4.8 %. Dual-energy X-ray absorptiometry was available for 58 patients, and 41.2 % had a T-score ≤ -2.5 standard deviation (lumbar spine and/or femoral neck and/or total hip). Only six (17.6 %) patients with a normal or osteopenic BMD were classified at high risk by the FRAX® BMD (bone mineral density). The NOF thresholds could only identify fewer than half of the studied population to be at high risk the day before an actual OF, and the 10-year hip fracture probability seemed to perform better than the 10-year major fracture probability. Prospective population-based studies are needed to validate the prediction of Chinese FRAX® model and to establish ideal thresholds.

Patients with familial hypercholesterolemia (FH) are often characterized by premature coronary artery disease (CAD) with heterogeneity at onset. The aim of the present study was to investigate the associations of lipoprotein (a) [Lp(a)] with the FH phenotype, genotype and roles of Lp(a) in determining CAD risk among patients with and without FH.We enrolled 8050 patients undergoing coronary angiography, from our Lipid clinic. Clinical FH was diagnosed using the Dutch Lipid Clinic Network criteria. Mutational analysis (LDLR, APOB, PCSK9) in definite/probable FH was performed by target exome sequencing.Lp(a) levels were increased, with a clinical FH diagnosis (unlikely, possible, definite/probable FH) independent of the patients status, with Lp(a)-hyperlipoproteinemia [Lp(a)-HLP] (median 517.70 vs. 570.98 vs. 604.65 mg/L, p 0.001) or without (median 89.20 vs. 99.20 vs. 133.67 mg/L, p 0.001). Patients with Lp(a)-HLP had a higher prevalence of definite/probable FH than those without (6.1% vs. 2.4%, p 0.05). However, no significant difference in Lp(a) was observed in patients with definite/probable FH phenotype carrying LDLR or LDLR-independent (APOB, PCSK9) or neither mutations (p 0.05). Multivariate analysis showed that Lp(a) and FH phenotype were both significant determinants in predicting the early onset and severity of CAD. Subsequently, patients with Lp(a)-HLP in definite/probable FH increased significantly the CAD risk (all p 0.05).Lp(a) levels were higher in patients with FH phenotype than in those without, but no difference were found in FH patients of different mutated backgrounds. Moreover, Lp(a) and FH played a synergistic role in predicting the early onset and severity of CAD.

Whether long non-coding RNA (lncRNA) single-nucleotide polymorphisms (SNPs) affect prognosis of acute myeloid leukemia (AML) remains unknown. To search the association between lncRNA SNPs and AML outcomes, thirty tagSNPs in five lncRNAs were genotyped in 313 AML patients. Survival analysis indicated that GAS5 rs55829688 (T C) was significantly associated with prognosis of AML (p = 0.018). Patients with rs55829688 CC genotype showed higher GAS5 expression in peripheral blood mononuclear cells (PBMCs) (p = 0.025) and harbored a longer platelets recovery (p = 0.040) than carriers of rs55829688T allele. In vitro study indicated that GAS5 promoter harboring the rs55829688C allele showed marginally increased reporter gene activity (p = 0.019), and the promoter activity was increased by TP63 in a dose-dependent manner (P = 0.001). Moreover, GAS5 higher expression predict shorter AML overall survival (OS), which validated in GEO GSE12417 dataset (p = 0.011). In conclusion, rs55829688 polymorphism could increase GAS5 expression by interacting with TP63, which might aggravate the myelosuppression and in turn lead to poor prognosis in AML. Trail registration number: ChiCTR-PPC-14005297.

Background It has been demonstrated that an elevated ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a risk factor of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM) and is also found to be associated with cardiovascular events (CVEs) in the general population. However, its prognostic value in patients with T2DM along with CAD remains to be determined. Materials and Methods A total of 1,447 consecutive patients with T2DM with angiographic-proven stable CAD were enrolled in the present study and followed-up for an average of 20.3 months. The characteristics of all patients including fasting lipid profile were obtained at baseline and multivariate Cox proportional hazards models were constructed using log TG/HDL-C as a predictor variable. The relationships between CVEs and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non–HDL-C, TC/HDL-C, LDL-C/HDL-C and apolipoprotein B/ apolipoprotein AI (apoB/apoAI) were also explored. Results Compared with patients without CVEs, the ones who experienced CVEs had a higher TG/HDL-C ratio. Univariable regression revealed a significant association of log TG/HDL-C with CVEs (hazard ratio = 2.5, P = 0.015). After adjusting for multiple traditional risk factors of cardiovascular disease, the association was still found (hazard ratio = 2.47, P = 0.047). Moreover, results suggested that the ratios of non–HDL-C, TC/HDL-C, LDL-C/HDL-C and apoB/apoAI were not predictors for CVEs in T2DM. Conclusions In our primary study, data suggested that elevated TG/HDL-C value might be a useful predictor for future CVEs in Chinese patients with T2DM with stable CAD. Further study is needed to confirm our findings.

Objective The study was designed to evaluate the role of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in ischemia-reperfusion injury (IRI) and acute rejection (AR) in rat intestinal transplantation, by administration of nitric oxide inhibitor NG-nitro-L-arginine methyl ester (LNAME). Materials and methods Rats that underwent orthotopic intestinal transplantation were assigned to 2 sets of groups: (1) iso-geneic group (Lewis-Lewis), L-NAME 0 mg/kg/d group (1-1), 4 mg/kg/d (group 1-2), or 8 mg/kg/d (group 1-3) injected intraperitoneally or (2) allogeneic group (Dark Agouti-Lewis), L-NAME 0 mg/kg/d (group 2-1) or 8 mg/kg/d (group 2-2) injected intraperitoneally. We examined survival times, light microscopy as well as maltose absorption tests. The nNOS and iNOS activities were measured by immunohistochemical methods. Results Histologic examination showed inhibited iNOS activity compared with group l-l, and Park scores decreased significantly in group 1-2 at 30 minutes after reperfusion (1.42 ± 0.38 vs 2.58 ± 0.49, P < .01). Both iNOS and nNOS activities were inhibited and Park scores increased significantly in group 1-3 from 30 minutes to day 3 after reperfusion (P

Objective Interleukin (IL)-33 is a cytokine belonging to the IL-1 family and was recently identified as a ligand for ST2, which belongs to the IL-1 receptor (IL-1R) family. In this study, we aimed to investigate the possible pathophysiological role of IL-33/sST2 in ankylosing spondylitis (AS). Methods The levels of IL-33/sST2 and vascular endothelial growth factor in serum samples of 140 patients with AS and 90 controls were measured by enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate, C-reactive protein level, and human leukocyte antigen B27 were measured by standard laboratory techniques. Disease activity in AS was measured by the Bath Ankylosing Spondylitis Disease Activity Index. Hip involvement, peripheral arthritis, and eye involvement were also recorded. Results The serum levels of IL-33/sST2 were remarkably higher in the patients with AS than the healthy groups and significantly correlated with vascular endothelial growth factor and the Bath Ankylosing Spondylitis Disease Activity Index. The sST2 levels correlated with erythrocyte sedimentation rate, C-reactive protein, platelet, and human leukocyte antigen B27. Elevated levels of IL-33/sST2 were detected in the patients with peripheral arthritis, and sST2 were detected to be increased in the patients with hip involvement. By contrast, levels of IL-33 but not sST2 increased in the patients with eye involvement. Conclusion IL-33/sST2 may regulate the immunological or inflammatory process of AS.

Busulfan/cyclophosphamide (Bu/Cy) conditioning regimen has been widely used to treat cancer patients, while their effects on major internal organs in females are not fully understood. We treated female mice with Bu/Cy, and examined the histopathology of major internal organs on Day 30 after the treatment. The results show that Bu/Cy treatment affected the ovaries most extensively, while it had less effect on the spleen, lungs, and kidneys, and no effect on the heart, liver, stomach, and pancreas. To better understand the effect of Bu/Cy on the ovaries, we counted follicles, and determined the levels of ovarian steroids. The Bu/Cy-treated mice showed a reduction of primordial and primary follicles (P

Aim: The aim of this study was to investigate histological and biomechanical properties of oviduct anastomosis with 2-octyl cyanoacrylate (OCA) in the rabbit. Material and Methods: Sixty female rabbits were randomly divided equally into three groups: A (control), B (traditional catgut suture), and C (non-suture technique using OCA). After suture or OCA anastomosis, gross examination (adhesion formation) and histopathology (hematoxylin–eosin), ultrastructure (transmission electron microscopy), and biomechanics (bursting pressure) on para-anastomotic site were investigated on oviduct taken at 1 (A1, B1, C1) and 4 (A2, B2, C2) weeks, respectively. Results: Adhesion score in group B was more severe than that in groups A and C at 1 and 4 weeks. Histopathology showed that acute endosalpingitis in group B was the most intense at 1 week, followed by significantly more tissue stimulation induced by catgut and foreign-body giant cells in group B than in group C at 4 weeks. Ultrastructural damage of ciliated cells was reversed partly (B2) and completely (C2) at 4 weeks. Bursting pressure in C1 was weaker than that in B1, followed by no significant difference at 4 weeks. Conclusion: Non-suture using OCA for oviduct anastomosis can be accepted as a new-perspective technique.

Purpose To compare the analgesic effect of preoperative ropivacaine with or without tramadol for femoral nerve block in total knee arthroplasty (TKA). Methods 14 men and 46 women aged 59 to 80 years who were American Society of Anesthesiologists (ASA) grade I or II and were scheduled for TKA were randomised to receive preoperative femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 0 mg (n=15), 50 mg (n=15), or 100 mg (n=15), or no preoperative femoral nerve block (control) [n=15]. Femoral nerve block was performed by a single anaesthesiologist before the standardised combined spinal epidural anaesthesia. Postoperatively, patient-controlled analgesia was given. The visual analogue score (VAS) for pain at rest and on movement was recorded at 8, 12, 24, 48, and 72 hours. Passive knee range of motion (ROM) was measured at 24, 48, and 72 hours. Results The 4 groups were comparable in terms of age, gender, weight, ASA grade, and operating time. Compared with patients who received no femoral nerve block or ropivacaine alone, those who received femoral nerve block with 20 ml of 0.375% ropivacaine plus tramadol 50 mg or 100 mg recorded a lower VAS for pain at rest and on movement at 8 to 72 hours, longer sensory and motor block time, and lower demand, delivery, and total amount of patient-controlled analgesia. The passive knee ROM at 24 to 72 hours was greater in patients with femoral nerve block than in those without. Conclusion Preoperative femoral nerve block with 20 ml of 0.375% ropivacaine and 100 mg tramadol resulted in the best analgesic effect.

We investigated simultaneously traditional and novel lipid indices, alone or in combination, in predicting coronary severity assessed by Gensini score (GS) in 1605 non-lipid-lowering-drug-treated patients undergoing coronary angiography. Firstly, levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), non high density lipoprotein cholesterol (non-HDL-C), apolipoprotein (apo) B, lipoprotein (a) [Lp(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC3, small dense LDL (sdLDL) and large HDL were increased, while HDL-C and apoA1 levels were decreased as GS status (all p for trend

Familial hypercholesterolemia (FH) is marked by an elevated plasma cholesterol and risk of premature cardiovascular disease. An increased burden of FH is being realized.To provide data on FH in Chinese patients with myocardial infarction (MI) and its potential contribution to early MI.A total of 1843 consecutive patients undergoing coronary angiography with their first MI were recruited. The clinical FH was diagnosed using the Dutch Lipid Clinic Network criteria. The prevalence and clinical features of FH and the relationship of FH to risk of early MI were investigated.Of the 1843 patients, 48.2% were detected as premature MI (pMI, the onset age ≤55 years for men, ≤60 years for women). The prevalence of definite/probable FH reached 3.9% (7.1% in pMI and 0.9% in non-pMI). Furthermore, we found that the risk of pMI was significantly elevated in both definite/probable FH (vs. unlikely FH, odds ratio, 5.05 [1.10-23.23]) and possible FH (vs unlikely FH, odds ratio, 2.65 [1.22-5.77]), independently from classical risk factors and medications. Additionally, patients with definite/probable FH occurred 10 years younger than those with unlikely FH in the onset age of MI (48.63 ± 1.20 vs 58.35 ± 0.30 years, P .001). When considered in subgroup of pMI or non-pMI, an early onset of MI was also observed in definite/probable FH (pMI, 45.83 ± 0.89 vs 47.87 ± 0.34 years; non-pMI, 60.75 ± 1.96 vs 65.07 ± 0.22 years; both P .05).The prevalence of FH among Chinese patients with MI appeared common, particularly among those with pMI. The phenotypic FH might significantly promote the early onset of MI.

Objective— Familial hypercholesterolemia (FH) is characterized by an elevated low-density lipoprotein cholesterol and increased risk of premature coronary artery disease. However, the general picture and mutational spectrum of FH in China are far from recognized, representing a missed opportunity for the investigation. Approach and Results— A total of 8050 patients undergoing coronary angiography were enrolled. The diagnosis of clinical FH was made using Dutch Lipid Clinic Network criteria, and the information of relatives was obtained by inquiring for the probands or from their own medical records of certain clinics/hospitals. Molecular analysis of FH was performed using target exome sequencing in LDLR (low-density lipoprotein cholesterol receptor gene), APOB (apolipoprotein B gene), and PCSK9 (proprotein convertase subtilisin/kexin type 9 gene). As a result, 3.5% of the patients with definite/probable FH phenotype (definite 1.0% and probable 2.5%) were identified. Women FH had fewer premature coronary artery disease (women P P Conclusions— We showed firsthand a common identification but poor treatment of patients with FH phenotype in Chinese coronary angiography patients. Genetic data in our FH cases might contribute to update the frequency and spectrum of Chinese FH scenarios.

Background Remnant cholesterol (RC) is receiving increasing attention regarding its relation to cardiovascular risk. Whether RC is associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in type 2 diabetes (T2D) is currently unknown. Methods We prospectively enrolled 1182 consecutive T2D patients who were scheduled for PCI but with baseline normal preprocedural cardiac troponin I (cTnI). Patients were divided according to their glycemic control status: group A [glycated hemoglobin (HbA1c) n = 563] and group B (HbA1c ≥ 7%, n = 619). PMI was evaluated by cTnI analysis within 24 h. The associations of preprocedural RC and the RC to high-density lipoprotein cholesterol ratio (RC/HDL-C) with PMI were investigated. Results The associations of RC and RC/HDL-C with PMI were observed in group B (both p p > 0.05). Patients in group B, a 1-SD increase of RC produced 30% and 32% increased risk for postprocedural cTnI > 3× upper limit of normal (ULN) and >5 × ULN, respectively. The odds ratios for RC/HDL-C were the highest compared with any cholesterol fractions including total cholesterol (TC)/HDL-C, low density lipoprotein cholesterol (LDL-C)/HDL-C, nonHDL-C/HDL-C, and triglyceride/HDL-C with 1.43 [95% confidence interval (CI): 1.10–1.88] for >3× ULN and 1.49 (95% CI: 1.13–1.97) for >5× ULN. However, no such associations were found in group A. Furthermore, patients with RC >27.46 mg/dL (third tertile) [RC ≤ 14.15 mg/dL (first tertile) as reference] were associated with a 1.57-fold and 2-fold increased risk for >3× ULN and >5× ULN in group B, respectively. Conclusions RC and RC/HDL-C might be valuable, independent predictors for PMI in poorly-controlled diabetic patients undergoing PCI.

Background High levels of pro-inflammatory cytokines in leukocyte- and platelet-rich plasma (L-PRP) may activate the nuclear factor κB (NF-κB) pathway to counter the beneficial effect of the growth factors on bone regeneration. However, to date, no relevant studies have substantiated this. Methods L-PRP and pure platelet-rich plasma (P-PRP) were isolated. The in vitro effects of L-PRP and P-PRP on the proliferation, viability and migration of human bone marrow-derived mesenchymal stem cells (HBMSCs) and EaHy926, tube formation of EaHy926, and osteogenic differentiation of HBMSCs were assessed by cell counting, flow cytometry, scratch assay, tube formation assay, and real-time quantitative polymerase chain reaction (RT-PCR), western blotting and Alizarin red staining, respectively. The in vitro effects of L-PRP and P-PRP on the nuclear translocation of NF-κB p65, mRNA expression of inducible nitric oxide synthase and cyclooxygenase-2, and production of prostaglandin E2 and nitric oxid were assessed by western blotting, RT-PCR, enzyme-linked immunosorbent assay and Griess reaction, respectively. The in vivo effects of L-PRP or P-PRP preprocessed β-tricalcium phosphate (β-TCP) on the calvarial defects in rats were assessed by histological and immunofluorescence examinations. Results P-PRP, which had similar platelet and growth factors concentrations but significantly lower concentrations of leukocytes and pro-inflammatory cytokines compared with L-PRP, promoted the proliferation, viability and migration of HBMSCs and EaHy926, tube formation of EaHy926 and osteogenic differentiation of HBMSCs in vitro, compared with L-PRP. The implantation of P-PRP preprocessed β-TCP also yielded better histological results than the implantation of L-PRP preprocessed β-TCP in vivo. Moreover, L-PRP treatment resulted in the activation of the NF-κB pathway in HBMSCs and EaHy926 in vitro while the postoperative delivery of caffeic acid phenethyl ester, an inhibitor of NF-κB activation, enhanced the histological results of the implantation of L-PRP preprocessed β-TCP in vivo. Conclusions Leukocytes in L-PRP may activate the NF-κB pathway via the increased pro-inflammatory cytokines to induce the inferior effects on bone regeneration of L-PRP compared with P-PRP. Hence, P-PRP may be more suitable for bone regeneration compared with L-PRP, and the combined use of P-PRP and β-TCP represents a safe, simple, and effective alternative option for autogenous bone graft in the treatment of bone defects.

Azathioprine (AZA) is widely used to treat Crohn's disease (CD) with a recommended dose of 2-2.5 mg/kg per day for Westerners. Asian patients are suggested to take a lower dose. However, many clinicians reported poor efficacy with a reduced dose. This study aimed to explore a efficient and safe dose of AZA providing the best efficacy for Chinese CD patients.Fifty patients with active CD were enrolled and randomized into two groups (n = 25 each). All other treatments were the same except that group A received 1 mg/kg per day and group B took 2 mg/kg per day of AZA. Complete remission (CR) rate and response rate at weeks 12, 24 and 48 were assessed by using intent-to-treat (ITT) and per-protocol (PP) analyses. Adverse events and recurrence rate were also evaluated.At week 48, CR rate and response rate in group B (ITT: 50.0% and 59.1%; PP: 57.9% and 68.4%) were significantly higher than those in group A (ITT: 13.0% and 17.4%; PP: 16.7% and 22.2%) (P 0.05). Nine adverse events occurred, including pancreatitis (n = 1), arthritis (n = 2) and myelosuppression (n = 6). There was no significant difference in adverse events between the two groups. However, recurrence rate was significantly higher in group A than in group B (P = 0.042).AZA 2 mg/kg per day is more appropriate than 1 mg/kg per day for Chinese CD patients with a high efficacy, a low recurrence rate and not increased adverse events.

Coronary artery disease (CAD) in very young individuals is a rare disease associated with poor prognosis. However, the role of specific lipoprotein subfractions in very young CAD patients (≤45 years) is not established yet. A total of 734 consecutive CAD subjects were enrolled and were classified as very early (n = 81, ≤45), early (n = 304, male: 45–55; female: 45–65) and late (n = 349, male: >55; female: >65) groups. Meanwhile, a group of non-CAD subjects were also enrolled as controls (n = 56, ≤45). The lipoprotein separation was performed using Lipoprint System. As a result, the very early CAD patients have lower large high-density lipoprotein (HDL) subfraction and higher small low-density lipoprotein (LDL) subfraction (p

Background and objective There is no consensus concerning small bowel preparation before capsule endoscopy (CE). This study evaluated the effects of 4 regimens on small bowel cleansing and diagnostic yield. Methods Patients were randomly divided into 4 groups. Group A consumed a clear liquid diet after lunch on the day before CE, followed by overnight fasting. Group B took 250 mL 20% mannitol and 1 L 0.9% saline orally at 05:00 hours on the day of the procedure. In group C, the same regimen was taken at 20:00 hours on the day before and at 05:00 hours on the day of CE. In group D, in addition to the group C regimen, 20 mL oral simethicone was taken 30 minutes before CE. Results Two hundred patients were prospectively enrolled, and 7 were excluded from the final analysis because of incomplete small bowel transit. No significant difference was noted among the 4 groups for small bowel transit time. Bowel preparation in group D was significantly better than for the other regimens for overall cleansing of the proximal small bowel, and showed improved overall cleansing of the distal small bowel when compared with 10-hours overnight fasting. Pathological lesions of the proximal and distal small bowel were, respectively, achieved in 82 and 74 patients, mostly distributed in group D. Conclusions Small bowel preparation that involves split-dose oral mannitol plus single-dose simethicone for CE can improve mucosal visualization and subsequent diagnostic yield when compared with 10-hours overnight fasting.

OBJECTIVE The purposes of this study were to describe the ultrasonographic findings in hepatic tuberculosis (TB) after administration of a second-generation sulfur hexafluoride-filled microbubble contrast agent and to correlate these findings with pathologic characteristics. METHODS Twenty-four hepatic TB lesions in 15 patients were studied with conventional ultrasonography (CUS) and contrast-enhanced ultrasonography (CEUS). Pathologic characteristics of the lesions were evaluated and were then correlated with enhancement patterns. RESULTS The appearance of hepatic TB on CUS was variable and nonspecific with respect to the shape, echogenicity, and boundary of the lesions. The diameters of the lesions obtained from CEUS were statistically larger than those from CUS, with largest diameters +/- SD of 4.2 +/- 1.8 and 3.1 +/- 1.9 cm, respectively. During the arterial phase, 13 of 24 lesions (54.2%) showed a rapidly and markedly enhanced rim with a hypoenhanced or nonenhanced center; 9 of 24 lesions (37.5%) showed transient enhancement of the whole lesion with inconsistent intensities. During the portal phase, most lesions showed distinct wash-out of the contrast agent and maintained a hypoechoic appearance. Pathologic studies confirmed that the different appearances of hepatic TB on CEUS were related to the different pathologic stages of the lesions. CONCLUSIONS Findings of hepatic TB on CEUS may be helpful in differentiating the diagnosis from other hepatic focal lesions. Correlation with pathologic findings would enrich the understanding of CEUS findings in hepatic TB.

Introduction: Propofol infusion syndrome (PRIS) is a rare but potentially fatal complication of propofol infusion. It is clinically characterized by metabolic acidosis, refractory bradycardia, rhabdomyolysis, renal failure, hyperlipidemia, and hepatomegaly. Brain lesion was only reported once in a pediatric patient. We present the 1st adult case with colon polyp and cancer who was diagnosed with PRIS. Her brain magnetic resonance imaging (MRI) and computed tomography (CT) scans reveal prominent bilateral brain lesions, matching with the proposed pathophysiologic mechanism of the syndrome. The patient received prompt acidosis correction and cardiorespiratory support. At last, she died from refractory circulatory failure. Conclusion: It may be necessary to order a prompt neuroimaging examination in patients suspected with PRIS to judge whether brain lesions exist or not.

Both increased lipoprotein-associated phospholipase A2 (Lp-PLA2) concentrations and atherogenic lipoprotein subfractions have been shown to reflect unfavourable cardiovascular risk. However, the correlation between Lp-PLA2 and lipoprotein subfractions in patients with coronary artery disease (CAD) has not been assessed yet.A total of 324 consecutive subjects who were not treated with lipid-lowering drugs were enrolled (angiographically proven CAD: n = 253; non-CAD: n = 71). Plasma Lp-PLA2 concentrations were measured using ELISA. The low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were determined by Lipoprint System.Plasma Lp-PLA2 concentrations were higher in patients with CAD compared with those without CAD (153.61 ± 78.73 vs. 131.41 ± 65.49 ng/ml, p = 0.028). The univariable correlation analysis revealed that Lp-PLA2 concentrations were positively correlated with the cholesterol concentrations of each LDL subfractions and the intermediate as well as small HDL subfractions, while negatively linked with the LDL particle size and large HDL-cholesterol (HDL-C) concentrations in CAD group. However, no similar results were observed in the non-CAD group. Furthermore, multivariable regression analysis was performed in patients with CAD and showed that plasma Lp-PLA2 concentrations were independently correlated with the cholesterol concentrations of each LDL subfractions [large LDL-cholesterol (LDL-C): β = 0.263, p0.001; intermediate LDL-C: β = 0.327, p0.001; small LDL-C: β = 0.135, p = 0.033] and small HDL-C (β = 0.133, p = 0.034).Lp-PLA2 concentrations were positively associated with all LDL subfractions and small HDL subfraction, suggesting an interaction between Lp-PLA2 and lipoprotein subfraction phenotypes in the status of CAD.

Background The relation of lipoprotein subfractions with stable coronary artery disease (CAD) has not been fully investigated in the Chinese Han population. Methods Four-hundred-and-thirteen consecutive patients without any lipid-lowering drug treatment were investigated. Patients were classified into two groups according to the angiographic results: CAD group (n=293) and non-CAD group (n=120). The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions were analysed using the Quantimetrix Lipoprint system. Results The data showed that the large HDL-cholesterol (HDL-C) level, large HDL subfraction percentage, and mean LDL particle size were significantly lower, while the small HDL-C level and HDL subfraction percentage, intermediate and small LDL-cholesterol (LDL-C) levels, and LDL subfraction percentages were higher in the CAD group compared with those in the non-CAD group. Interestingly, our results suggested that the small HDL-C level and HDL subfraction percentage as well as mean LDL particle size were independently associated with the presence of CAD assessed by logistic regression analysis (OR=1.136, 95%CI=1.018-1.268, p=0.022; OR=1.076, 95%CI=1.021-1.134, p=0.007; OR=0.946, 95%CI=0.898-0.997, p=0.040; respectively). Conclusions Similar to previous Western population studies, our data suggested a clear association between the lipoprotein subfractions and stable CAD presented as higher small HDL subfraction and smaller mean LDL particle size in Chinese Han patients.

Background Recent data showed inconsistent association of high‐density lipoprotein cholesterol ( HDL ‐C) with cardiovascular risk in patients with different levels of low‐density lipoprotein cholesterol ( LDL ‐C) or intensive statin therapy. This study sought to determine the relationship of HDL ‐C with periprocedural myocardial injury following elective percutaneous coronary intervention ( PCI ) across a range of LDL ‐C levels, especially in patients with LDL ‐C dL . Methods and Results We enrolled 2529 consecutive patients with normal preprocedural cardiac troponin I ( cTnI ) who underwent elective PCI . The association between preprocedural HDL ‐C and periprocedural myocardial injury was evaluated across LDL ‐C levels, especially in patients with LDL ‐C dL . The HDL ‐C level was not predictive of periprocedural myocardial injury across the entire study cohort. However, among patients with LDL ‐C dL , a 1 mg/ dL increase in HDL ‐C was associated with a 3% reduced risk for postprocedural cTnI above 1×upper limit of normal ( ULN ) (odds ratio: 0.97; 95% CI : 0.95 to 0.99; P =0.004), a 3% reduced risk for postprocedural cTnI above 3× ULN odds ratio: 0.97; 95% CI : 0.95 to 0.99; P =0.022), and a 3% reduced risk for postprocedural cTnI above 5× ULN (odds ratio: 0.97; 95% CI : 0.95 to 0.99; P =0.017). The relation between plasma HDL ‐C level and risk of postprocedural cTnI elevation above 1× ULN , 3× ULN , and 5× ULN was modified by LDL ‐C level (all P for interaction Conclusions Higher HDL ‐C levels were associated with reduced risk of periprocedural myocardial injury only in patients with LDL ‐C dL .

The purpose was to study the performance of expandable proximal femoral nails (EPFNs) for the treatment of unstable intertrochanteric fractures in elderly patients.Eighty-four patients were treated with a newly designed EPFN and followed up for one year.The mean operating time was 50.1 ± 3.2 min and the mean blood loss was 112.3 ± 5.3 ml. Patients were treated with EPFNs of 220 mm (n = 24), 240 mm (n = 59), and 340 mm (n = 1) length. At six months postoperatively, the Harris Hip Score was 74.5 ± 5.3. At the end of follow up, 75% of patients completely recovered their preoperative function and resumed their normal activities. Seven patients died within one year postoperatively. During the operation, one patient experienced proximal femoral diaphyseal slight crack fracture. This crack fracture was treated by using a long EPFN (340 mm). Two patient developed screw cut-outs, which were solved by reoperation. And one developed deep infection resolved favorably by the appropriate antibiotic treatment. Implant failure, deep venous thrombosis, fat embolism, secondary fracture, and nonunion were not encountered.In conclusion, the results of the EPFNs were satisfactory in most elderly patients with unstable intertrochanteric fracture. However, during the inflation period, the pressure on the nail must be monitored carefully in order to prevent a crack fracture.

Background Plasma PCSK9 levels was positively associated with low-density lipoprotein (LDL) cholesterol (LDL-C) and atherosclerosis, while PCSK9 may also be implicated in the metabolism of lipoprotein subfractions. The study was to examine the association of plasma PCSK9 with lipoprotein subfractions in patients with stable coronary artery disease (CAD). Methods A total of 281 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled. The baseline clinical characteristics were collected, the plasma PCSK9 levels were determined using ELISA, and the LDL and high-density lipoprotein (HDL) subfractions were analyzed by Lipoprint System. The association of plasma PCSK9 levels with the lipoprotein subfractions was investigated. Results In the overall population, plasma PCSK9 levels were positively associated with the concentration of LDL-C, intermediate LDL-C, small LDL-C, and LDL score, while negatively correlated with mean LDL particle size. PCSK9 levels were positively associated with the concentration of HDL-C, intermediate HDL-C and small HDL-C. Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the concentration of intermediate LDL-C (β = 0.152, p = 0.013), small LDL-C (β = 0.179, p = 0.004), LDL score (β = 0.121, p = 0.043), and mean LDL particle size (β = -0.130, p = 0.035), while not HDL subfractions. Interestingly, when investigated in male and female patients separately, these relationships were only found in male but not in female, and the small HDL-C exhibited an association with PCSK9 levels in male patients (β = 0.149, p = 0.045). Conclusions PCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD.

Objectives The aim of this study was to investigate the association of serum fibrinogen with cardiovascular events (CVE) in Chinese patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD). Design An observational study. Setting FuWai Hospital in Beijing, China. Participants A cohort of 1466 patients with T2DM and angiographic-proven stable CAD was evaluated. Outcome measures Baseline serum fibrinogen levels were measured and trisected into ‘low’, ‘middle’ and ‘high’. Their association with CVE was explored using Cox proportional hazard models. Results With 20.2 months (average) follow-up, 44 (3%) were lost to follow-up and 96 patients developed CVE. Compared with the patients without CVE, the ones who developed CVE had higher levels of fibrinogen. Univariable regression revealed a significant relation of fibrinogen to CVE (HR (HR) 1.25, 95% CI 1.06 to 1.47, p=0.010) per SD increase of fibrinogen at baseline. After adjusting for multiple established cardiovascular disease (CVD) risk factors, the association persisted (HR 1.30, 95% CI 1.02 to 1.66, p=0.037). Moreover, after adjusting for CVD risk factors, the HRs for middle-serum and high-serum fibrinogen concentration, using ‘low’ group as reference, were 1.23 (95% CI 0.69 to 2.20) and 2.20 (95% CI 1.11 to 3.36, p=0.049). Conclusions We first indicated that elevated fibrinogen level was independently associated with increased CVE in Chinese patients with T2DMand stable CAD.

a Center for Dyslipidemia and Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing 100037, China b Department of Cardiology, The Fifth Hospital of Wuhan & Affiliated Guangci Hospital of Wuhan University, Wuhan 430050, China

Objectives: To assess the prognostic value of coexisting coronary artery disease (CAD), Markis class, and ectasia ratio for major adverse cardiovascular events in patients with coronary artery ectasia (CAE). Methods: A total of 512 consecutive patients with angiographically proven CAE were enrolled. Coronary ectasia extent was graded using the Markis class, and ectasia severity was assessed based on the ectasia ratio. Patients were followed up for a median of 34.6 months. Results: In the current study, 76 cases had isolated CAE, while the remaining 436 cases had coexisting CAD (mixture CAE). Males (84.4%) were predominantly affected, and the right coronary artery (55.1%) was most commonly involved. During follow-up, 86 overall major adverse cardiovascular events were diagnosed. Kaplan-Meier analysis failed to reveal any differences between isolated and mixture CAE in both cumulative and event-free survival analyses (p = 0.429 and p = 0.277, respectively). Moreover, when patients were divided into 4 groups according to Markis class (type I-IV) or 2 groups based on the ectasia ratio (1.5-2.0 and >2.0), there was no significant difference in survival outcomes among the groups (p > 0.05). Conclusions: In this follow-up study with a relatively large sample, the survival rate of patients with CAE appeared to be independent of coexisting CAD and ectasia extent and severity.

To explore the efficacy and safety of zero-profile implant for anterior cervical discectomy and fusion (ACDF) in treating single cervical disc herniation.From August 2011 to June 2012,30 patients with single cervical disc herniation were treated with ACDF using zero-profile implant in one motion segment. There were 18 males and 12 females with a mean age of 55.3 years old (ranged, 36 to 68). Incidence of dysphagia, height of intervertebral space and condition of bone fusion were observed after operation. Spinal nerves function and clinical results were assessed according to Japanese Orthopaedic Association (JOA) score, Odom criteria.All patients were followed up from 12 to 24 months with an average of 15.9 months. The mean intraoperative blood loss was (85.3 +/- 14.2) ml (70 to 120 ml) and operative time was (90.0 +/- 12.8) min (70 to 120 ml). Preoperative, postoperative at 3 months and 1 year, JOA score was 8.72 +/- 2.36 (5.0 to 13.0), 14.72 +/- 1.66 (11.5 to 17.0) and 15.65 +/- 1.03 (13.5 to 17.0), respectively. One year after operation, according Odom criteria to assess, 22 cases got excellent results, 7 good, 1 fair. All dysphagiaes vanished completely at 3 months after operation. The lost height of intervertebral space was (0.34 +/- 0.13) mm (0.1 to 0.6 mm) and (0.39 +/- 0.15) mm (0.2 to 0.7 mm) at 3, 12 months after operation, respectively. All patients obtained bone fusion at 1 year after operation.The zero-profile implant is a valid alternative to anterior cervical plate in treating single cervical disc herniation with ACDF, it has advantages of convenient procedure, satisfactory effect, lower incidence of postoperative dysphagia, reliable stability and less implant-related complications.

Objective : Non-HDL cholesterol (non-HDL-C) has recently been recommended as a first target for dyslipidemia management. We previously reported that LDL cholesterol (LDL-C) and non-HDL-C levels were similarly associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in patients with coronary artery disease. Here we investigated the comparative prognostic value of non-HDL-C and LDL-C for PMI following PCI in type 2 diabetes (T2D). Methods : We prospectively enrolled 1194 consecutive T2D patients with normal preprocedural cTnI undergoing PCI. Patients were divided into the two groups: group A [glycated hemoglobin (HbA1c) n = 567] and group B (HbA1c ≥ 7%, n = 627). PMI was evaluated by cTnI analysis within 24 h. The relationship of preprocedural non-HDL-C and LDL-C levels with peak cTnI values after PCI was examined. Results : Patients in group B, with higher preprocedural non-HDL-C levels, had higher postprocedural cTnI levels ( β = 0.102, P = 0.011). In the multivariable model, a 1-SD increase in non-HDL-C produced a 30% and 33% increased risk of postprocedural cTnI >3 × upper limit of normal (ULN) and >5 × ULN in group B, respectively. However, neither LDL-C nor group A patients were affected. Furthermore, patients with non-HDL-C levels ≥130 mg/dl compared with non-HDL-C levels ≤100 mg/dl were associated with a 83.3% and 71.7% increased risk of postprocedural cTnI >3 × ULN and >5 × ULN in group B, respectively. Conclusions : In poorly-controlled diabetic patients (HbA1c ≥ 7%) undergoing PCI, non-HDL-C but not LDL-C was independently associated with and increased risk of PMI, and non-HDL-C levels ≥130 mg/dl had a worse PMI risk profile compared with non-HDL-C levels