Search

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.

Replantation of a lower extremity amputated at the knee joint level in a child is rare. We present a case of a 3-year-old child with his right leg totally severed from the knee joint in a traumatic accident. After 5 hours of cold ischemia time, together with antishock therapies, the child underwent leg replantation under stable conditions. The replanted lower limb finally survived after several surgical procedures. The patient was discharged 4 weeks after admission and had restored partial motor and sensory functions 6 months after surgery. During follow-ups, the patient underwent sustained rehabilitation and recovered well. Two years after replantation, secondary knee reconstruction was performed and yielded favorable aesthetic and functional improvement. In brief, a successful knee-level replantation in a child is attributed to correct preoperative first aid, excellent microsurgical skills, and intensive postoperative management.

Introduction Peripheral Facial paralysis (PFP) results in functional and social dysfunction, when it is under a severe condition at onset, long-term poor outcomes do occur. Different acupuncture method has been reported to be potentially effective for shortening the disease course and reduce the occurrence of sequelae when applying at an early stage. Neuroedema is a common pathological feature in the acute phase, many clinical studies have suggested its effect of reducing facial nerve edema. It is of value to estimate the effectiveness and safety of acupuncture treatment at the onset, and it is worthwhile to assess the most suitable acupuncture method for the acute period. Methods and analysis We will include all the RCTs and quasi-RCTs on acupuncture therapy for PFP at its acute stage. Literature searching will be conducted until September 15th, 2020 from eight databases systematically. Two reviewers will screen the literature and extract the data independently. RevMan software and the Cochrane tool of Risk of Bias will be used to assess the methodological quality of RCTs. Forest plots and summary findings will be generated. If data permits, a meta-analysis will be conducted. Ethics and dissemination Since this study will not involve clinical treatment of patients, ethics approval is not required. The result of this study will be submitted to a peer-reviewed journal for publication and as a proposal for clinical practice and further study on acupuncture treatment at the early stage of PFP. Discussion This review will summarize the evidence on the different type of acupuncture therapy for acute bell’s palsy and Ramsay-Hunt syndrome. We anticipate that it would be safe and effective when applying to the acute phase of PFP, and some specific suitable acupuncture methods would be found resulting from this review.Trial registration number International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020205127

Background The optimal timing to perform a total knee arthroplasty (TKA) after knee arthroscopy (KA) was controversial in the literature. We aimed to 1) explore the effect of prior KA on the subsequent TKA; 2) identify who were not suitable for TKA in patients with prior KA, and 3) determine the timing of TKA following prior KA. Methods We retrospectively reviewed 87 TKAs with prior KA and 174 controls using propensity score matching in our institution. The minimum follow-up was 2 years. Postoperative clinical outcomes were compared between groups. Kaplan-Meier curves were created with reoperation as an endpoint. Multivariate Cox proportional hazards regressions were performed to identify risk factors of severe complications in the KA group. The two-piecewise linear regression analysis was performed to examine the optimal timing of TKA following prior KA. Results The all-cause reoperation, revision, and complication rates of the KA group were significantly higher than those of the control group (p p = 0.002), respectively. Male (Hazards ratio [HR] = 3.2) and prior KA for anterior cruciate ligament (ACL) injury (HR = 4.4) were associated with postoperative complications in the KA group. There was a non-linear relationship between time from prior KA to TKA and postoperative complications with the turning point at 9.4 months. Conclusion Prior KA is associated with worse outcomes following subsequent TKA, especially male patients and those with prior KA for ACL injury. There is an increased risk of postoperative complications when TKA is performed within nine months of KA. Surgeons should keep these findings in mind when treating patients who are scheduled to undergo TKA with prior KA.

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 The optimal time to perform a total knee arthroplasty (TKA) after knee arthroscopy (KA) was controversial in the literature. We aimed to 1) explore the effect of prior KA on the subsequent TKA; 2) identify who were not suitable for TKA in patients with prior KA; and 3) determine the timing of TKA following prior KA.Methods We retrospectively reviewed 87 TKAs with prior KA and 174 controls using propensity score matching in our institution. The minimum followup was 2 years. Postoperative clinical outcomes were compared between groups. Kaplan-Meier curves were created with reoperation as an end point. Multivariate Cox proportional hazards regressions were performed to identify risk factors of severe complications in the KA group. The two-piecewise linear regression analysis was performed to examine the optimal timing of TKA following prior KA.Results The all-cause reoperation, revision and complication rates of KA group were significantly higher than those of control group (pConclusion Prior KA is associated with worse outcomes following subsequent TKA, especially male patients and those with prior KA for ACL injury. There is an increased risk of postoperative complications when TKA is performed within 9 months of KA. Surgeons should keep these findings in mind when treating patients who are scheduled to undergo TKA with prior KA.

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: Previous studies have clearly demonstrated that XueZhiKang (XZK), an extract of cholestin, can decrease low-density lipoprotein cholesterol (LDL-C) and cardiovascular events. However, the mechanism of the effects of XZK on atherosclerosis (AS) in humans has been reported less frequently. In the present study, we investigated the impact of XZK on lipoprotein subfractions, oxidized LDL (oxLDL), and interleukin-6 (IL-6). Methods: From October 2015 to July 2016, 40 subjects were enrolled in this study. Of them, 20 subjects with dyslipidemia received XZK 1200 mg/day for 8 weeks (XZK group); 20 additional healthy subjects who did not receive therapy acted as controls. The plasma lipoprotein subfractions, oxLDL, and IL-6 were examined at baseline and again at 8 weeks. Results: Data showed that XZK could significantly decrease not only plasma LDL-C levels (87.26 ± 24.45 vs. 123.34 ± 23.99, 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.

BackgroundHypercholesterolemia is the accepted causal risk factor for atherosclerotic cardiovascular disease (ASCVD). 2013 ACC/AHA guideline on the treatment of cholesterol advised to tailor high-intensity statin for patients with coronary artery disease (CAD). However, its impact of real clinical practice has not been examined in China.MethodsIn this cross-sectional study, 3592 patients with CAD were consecutively enrolled who were receiving statins in outpatient department (at least 4weeks) before they were admitted to the ward at five University hospitals from April 2011 to December 2015. Patients were divided into two groups according to the admission time before (group A, n=1521) or after (group B, n=2071) online announcement date of 2013 ACC/AHA guideline. The situation of statin application and LDL-C target achievement (LDL-C

Objective Familial hypercholesterolemia (FH), an autosomal dominant genetic disorder, is often diagnosed in young age and cholesterol accumulation in tissues produces common clinical manifestations including cutaneous xanthomas, premature atherosclerosis, and poor response to medical therapy. The main objective was to investigate the patients of hoFH from China. Patients Over the past 4 years, a cohort of 8 patients with severe FH phenotype due to the characteristic cutaneous xanthomas and extremely high low density lipoprotein cholesterol (LDL-C) levels from the national lipid clinics were enrolled. Genotype information was obtained. Results Of them, 7 patients had severe coronary atherosclerosis, 6 had family history of hypercholesterolemia, 2 had family history of premature coronary atherosclerosis. The patients had untreated LDL-C of > 13 mmol/L, and received maximal medical therapy. Importantly but not surprisingly, the lipid profile was not significantly improved by the current available concomitant use of rosuvastatin and ezetimibe. In genetic analysis, all patients had the mutations responsible to the FH phenotype and showed to be more heterogeneous than their clinical phenotype. Conclusion In a conclusion, we found a relatively common recruitment of this type of patients in our hospital, which might have an important clinical implication for the identification and management of the patients with FH in China.

Objective Azathioprine (AZA) is widely used in Crohn's disease (CD) patients with a recommended dose, 2-2.5 mg/kg/d, for Westerners. Asian patients are suggested with a lower dose. However, many clinicians reported a poor efficacy with a reduced dose. Our prospective study aims to find a safe dose providing the best efficacy for Chinese CD patients. Methods Fifty active Chinese CD patients were enrolled in our test and randomly split into 2 groups, 25 each. All other treatments were the same except that group A took 1 mg/kg/d and group B took 2 mg/kg/d of AZA. We analysed the complete remission (CR) rate and the response rate on week 12, 24, 48 and with the method of intent-to-treat (ITT) and Per-Protocol (PP) analysis to evaluate the efficacy. Meantime, we evaluated the adverse events and the recurrence rate in both groups. Results On week 48, the 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

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.

Introduction Granulocytic sarcoma (GS) is a commonly occurring tumor comprising immature myeloid cells, which are usually related to acute or chronic myelocytic leukemia. The tumor rarely precedes leukemia without bone marrow involvement and is called primary GS. Although primary GS can occur in any body part, the involvement of the oral cavity is uncommon. Patient concerns A 49-year-old woman hospitalized at the Department of Plastic and Maxillofacial Surgery presented with a growing mass in her left maxillary hard palate dating two months back. No obvious physical findings were noted during general examination. She was diagnosed with an oral ulcer at a local clinic, and received antibiotics. However, the symptoms did not improve; the mass became bigger and painful. Diagnosis An incisional biopsy of the oral mass was performed, the immunohistochemistry showed that the tumor cells tested positive for myeloperoxidase, CD4, BCL-2, KI-67. Bone marrow aspiration was negative for malignant cells, and the laboratory test results revealed only monocytosis. Standard bone marrow cytogenetic analysis showed a normal karyotype and leukemia-related fusion gene detection was normal. Therefore, the final diagnosis was intraoral primary GS. Interventions The patient was treated with a chemotherapy regimen based on idarubicin and cytarabine arabinoside. Outcomes After 2 cycles of idarubicin and cytarabine arabinoside regimen chemotherapy, the patient achieved complete remission. The tumor was barely visible in the left maxillary hard palate. There has been no evidence of disease spread and progression after 1 year of follow-up. Conclusions Careful morphological and immunohistochemical analyses, correlating with clinical data are necessary to establish the diagnosis of oral primary GS. Early aggressive systemic chemotherapy can effectively relieve symptoms, significantly reducing primary GS conversion into acute myelocytic leukemia and prolonging overall survival.

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.

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]

Elevated preprocedural N-term pro-B-type natriuretic peptide (NT-pro-BNP) and postprocedural cardiac troponin I (cTnI) are related to a poor cardiac outcome in the non-diabetic population. We hypothesized that preprocedural NT-pro-BNP might be a useful marker in predicting periprocedural myocardial injury (PMI) following elective percutaneous coronary intervention (PCI) in type 2 diabetes (T2D).We prospectively enrolled 1194 consecutive diabetic patients with normal cardiac function and preprocedural cTnI who were successfully undergoing elective PCI. Preprocedural NT-pro-BNP levels were assessed at admission, and PMI was evaluated by analysis of cTnI within 24 hours. The relationship between preprocedural NT-pro-BNP levels and the peak values of cTnI after PCI was examined.Patients with high baseline NT-pro-BNP levels had higher postprocedural cTnI levels (β = 0.123, p0.001). In the multivariable model, NT-pro-BNP was associated with higher risk of postprocedural cTnI elevation above 1 × upper limit of normal (ULN, OR, 3.13; 95% CI, 1.51-6.50; p = 0.002), 3 × ULN (OR, 2.44; 95% CI, 1.17-5.08; p = 0.018), 5 × ULN (OR, 3.18; 95% CI, 1.44-7.0; p = 0.004), respectively. Moreover, the incidence of cTnI elevation was higher in patients with the upper tertile of NT-pro-BNP levels than that in ones with the lower tertile of NT-pro-BNP levels (1 × ULN: 63.1% vs. 50.0%, p0.001;3 × ULN: 39.2% vs. 31.9%, p = 0.032;5 × ULN: 30.4% vs. 21.9%, p0.006; respectively).Our data, for the first time, demonstrated that increased preprocedural NT-pro-BNP levels were strongly and independently associated with a higher risk of PMI, suggesting that baseline NT-pro-BNP level might be a useful marker for predicting PMI following PCI in diabetic patients without cardiac dysfunction.

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.

Aim This study aims to investigate the expression levels of elastin and lysyl oxidase (LOX) family members in the urogenital tissues of natural aging mice and accelerated ovarian aging mice. Method Uteri, vaginas and bladders were harvested from 18-month-old female mice and accelerated ovarian aging mice developed by chemotherapeutic agents. Untreated 3-month-old female mice were used as controls. The expression levels of elastin and LOX family members were determined by real-time polymerase chain reaction and western blot. Results Compared with untreated young female mice, the expression of elastin and LOX family members significantly decreased both in natural aging mice and accelerated ovarian aging mice. Conclusion Aging is a high-risk factor for pelvic floor disorders. The failure of elastic fiber synthesis and assembly due to the decline in expression levels of elastin and LOX family members during aging may explain the molecular mechanism causing pelvic floor disorders.

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.

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.

Over the past half-century, biomaterials have been used in orthopaedic surgery world widely, but orthopaedic implant-associated infections (OIAIs) are still a puzzle for orthopaedic surgeons, which may result in prolonged hospitalisation, poor functional status and high costs. The presence of implants increases the risk of microbial infection; moreover, the formation of bacterial biofilm leads to a higher resistance to antibiotics and local immune response. In such cases, conventional systemic delivery of drugs seems to be fairly inefficient and out-dated. Owing to this, debridement and/or removing the implant always become the only solution. Hence, it needs a simple, minimally invasive and effective therapy to eradicate the problem. There are abundant evidences showing that extracorporeal shock wave therapy (ESWT) has favourable effects on stimulating callus formation, inducing angiogenesis, promoting osteogenesis and relieving pain. Studies also indicated that ESWs have a significant bactericidal effect on bacterial strains of bone- and implant-associated infections. Therefore, a hypothesis proposed herein is that ESWT may well be an effective adjuvant treatment for OIAI by controlling infection, inducing bone regeneration and promoting re-osseointegration.

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

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

// Xiong-Yi Gao 1, 2, * , Bing-Yang Zhou 1, * , Min-Zhou Zhang 2, * , Xi Zhao 1 , Ping Qing 1 , Cheng-Gang Zhu 1 , Na-Qiong Wu 1 , Yuan-Lin Guo 1 , Ying Gao 1 , Xiao-Lin Li 1 , Yao Wang 1 , Geng Liu 1 , Qian Dong 1 , Li-Heng Guo 2 and Jian-Jun Li 1 1 Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China 2 Division of Chest Pain Center, Guangdong Provincial Hospital of Chinese Medicine, The 2nd Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China * These authors contributed equally to this work Correspondence to: Jian-Jun Li, email: lijianjun938@126.com Keywords: fibrinogen, myocardial infarction, coronary artery, very young patients, Gensini score Received: August 23, 2016 Accepted: May 21, 2017 Published: June 20, 2017 ABSTRACT Fibrinogen (Fib) is a useful marker for predicting the severity of coronary artery disease (CAD) in adult population. However, whether Fib can be a predictor for the presence and severity of CAD in very young MI patients (≤35 years old) remains to be determined. A total of 418 males from 61,863 patients with MI who were under 35 years old were sequentially recruited in our study. The patients were divided into two main groups and three subgroups according to coronary angiograph and Gensini score (GS) system: no coronary artery stenosis (group A), the results of the coronary artery stenosis (group B); low GS, intermediate GS and high GS. Data indicated that Fib, body mass index, current smoking, white blood cell count (WBCC) and GS were significantly higher in group B than those in group A (all P < 0.01). Moreover, there were significant differences in Fib, mean age, diabetes mellitus, family history of CAD, WBCC, left ventricular ejection fraction, and GS between high GS and low GS subgroups (all P < 0.01). A positive correlation between Fib levels and GS was found (r = 0.242, p < 0.001). Receiver operating characteristics curve analysis demonstrated that the best cut-off level of Fib predicting the severity of coronary stenosis was 3.475g/L (sensitivity 64%; specificity 70%) and the area under the curve was 0.656. Fib was also independently associated with high GS (OR=2.173, 95%CI 1.011–4.670, P = 0.047) after adjusting for potential confounders. In conclusion, Fib is significantly related to the presence and severity of coronary stenosis in male patients with MI under 35 years old.

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.

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

This study aimed to evaluate the role of combined use of rapamycin and leflunomide(Lef) on the prevention of acute allograft rejection in rats. After cardiac transplantations, rats were randomly divided into untreated group, rapamycin group, Lef group and rapamycin+Lef group. The drugs were given by gavage from day 0 to day 9 after transplantations. Graft survival time was observed. Some grafts were harvested for histopathological investigation on day 10 after transplantations. The levels of CD(4)(+) and CD(8)(+) T lymphocytes and the concentrations of interleukin 2(IL-2) and interferon (IFN)γ in peripheral blood were examined on day 10 after transplantations. At the same time, the body weight, the hepatic function, renal function and the haemoglobin of the recipients were also examined. The graft survival time of untreated group was 7.14 ± 1.07 days. Rapamycin group was 11.14 ± 1.35 days. Lef group was 11.29 ± 1.80 days. While in rapamycin+Lef group, the graft survival time was prolonged to 13.86 ± 1.57 days(P0.05). Histological changes of the allografts in rapamycin+Lef group were much milder than either of the two single drug groups. The absolute number and the percentage of CD(4)(+) T lymphocytes in peripheral blood in rapamycin+Lef group were lower than those of rapamycin or Lef group on day 10 after transplantations(P0.05), while the percentage of CD(8)(+) T lymphocytes in rapamycin+Lef group was higher than that of rapamycin or Lef group(P0.05). The absolute number of CD(8)(+) T lymphocytes was not significantly different among rapamycin group, Lef group and rapamycin+Lef group. The levels of IL-2 and IFN-γ in rapamycin+Lef group were significantly lower than that of rapamycin group or Lef group(P0.05). The body weight, the hepatic function, renal function and the haemoglobin were not significantly different among rapamycin group, Lef group and rapamycin+Lef group (P0.05). Combined use of rapamycin and Lef had better effect on the prevention of acute cardiac allografts rejection in rats than monotherapy.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver disease that is closely related not only to genetic susceptibility but also to insulin resistance and highly linked with metabolic syndrome. In recent years, the prevalence of NAFLD has increased rapidly, paralleling the epidemic of type 2 diabetes mellitus and obesity leading to cardiovascular disease. It has been demonstrated that NAFLD is highly associated with atherosclerosis. With recently gained knowledge, it appears that NAFLD may induce insulin resistance, dyslipidemia, oxidative stress, inflammation, and fluctuation of adipokines associated with atherosclerosis. In this review, we aimed to summarize recent discoveries related to both NAFLD and atherosclerosis, and to identify possible mechanisms linking them.

Objective To investigate the protective effect of compound Xueshuantong capsule against damage of diabetic nephropathy in rat diabetic model.Methods Male SD rats were given intraperitoneal injection of streptozotocin(STZ)at 60mg/kg, and diabetic rat model was deemed successfully induced when the blood glucose level≥16.7mmol/L 3days after injection.Thirty model rats were randomly divided into the following 3groups equally:diabetic model group(DM),compound Xueshuantongcapsule group(XST),andα-lipoic acid treatment group(ALA).Another 10normal rats served as normal control group(NG).The body weight,blood glucose,blood fat,kidney weight/body weight(KW/BW),24h-urinary protein excretion,urea nitrogen,and serum creatinine were observed and compared between different groups after 12weeks’treatment.The ultrastructure changes of kidney were observed by electron microscopy and light microscope.Results Compared with NG group,rats in DM group had a higher 24h-urinary protein excretion(P0.05),and those in XST group and ALA group had a significantly lower one compared with the DM group(P0.05).Compared with NG group,rats in the other 3groups had a higher KW/BW,with significant difference found between DM group and XST group(P0.05).Electron microscopic results showed uneven glomerular basement membrane thickening, foot process integration,and mesangial cell proliferation in the model group;all the above changes were improved in the XST and ALA groups.Conclusion Compound Xueshuantongcapsule can lower the 24h-urinary protein secretion,decrease KW/BW,and improve the structure of glomerular basement membrane,thus exerting renal protective effect in diabetic rats.

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.