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Grape seed proanthocyanidin extract (GSPE) that prevents and alleviates the degenerative changes associated with aging has been receiving extensive attention. In our present work, the ageing model was induced by injection of 500 mg kg

Background: N4-acetylcytidine (ac4C), an important posttranscriptional modification, is involved in various disease processes. Long noncoding RNAs (lncRNAs) regulate gene expression mainly through epigenetic modification, transcription, and posttranscriptional modification. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloidosis of the brain. However, the role of lncRNA ac4C modification in AD remains unclear. Objective: In this study, we investigated the association between ac4C modification and AD, and the underlying mechanisms of ac4C modification in AD. Methods: The male 9-month-old APP/PS1 double transgenic mice, age- and sex-matched wild type (WT) mice were used in this study. Then, ac4C-RIP-seq and RNA-seq were used to comprehensively analyze lncRNA ac4C modification in AD mice. The lncRNA-miRNA-mRNA regulatory networks using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed the regulatory relationships among these three lncRNAs and AD. Results: The results showed that there were 120 significantly different ac4C peaks located on 102 lncRNAs in AD, of which 55 were hyperacetylated and 47 were hypoacetylated. Simultaneously, 231 differentially expressed lncRNAs were identified, including 138 upregulated lncRNAs and 93 downregulated lncRNAs. Moreover, 3 lncRNAs, lncRNA Gm26508, lncRNA A430046D13Rik, and lncRNA 9530059O14Rik, showed significant changes in both the ac4C and RNA levels using conjoint analysis. Conclusion: The abundance of lncRNA ac4C modification is significantly different in AD and indicates that lncRNA ac4C is associated with the occurrence and development of AD, which could provide a basis for further exploration of the related regulatory mechanisms.

Background The detection rate of bilateral multiple pulmonary nodules (BMPNs) is increasing due to widespread use of chest computed tomography (CT) screening. However, there is no consensus on the treatment options for BMPNs and whether simultaneous bilateral pulmonary resection is safe remains controversial. The purpose of this study was to evaluate the feasibility and safety of simultaneous bilateral pulmonary resection for BMPNs. Methods A total of 16 consecutive patients with BMPNs who underwent simultaneous bilateral pulmonary resection in Beijing Hospital from June 2013 to July 2020 were enrolled in this study. Clinical characteristics, imaging and pathological features, and perioperative outcomes were retrospectively reviewed. Results There were 10 males and six females included in the study with a mean age of 61.9 (range: 39–78) years. A total of 35 nodules were resected in 16 patients including 12 patients with bilateral primary lung cancer, three patients with primary lung cancer on one side and a benign nodule on the contralateral side, and one patient with bilateral benign nodules. All patients underwent bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery (VATS). Nine, four, two, and one patients underwent lobectomy with contralateral segmentectomy or wedge resection, segmentectomy with contralateral wedge resection, bilateral segmentectomy and bilateral wedge resection, respectively. All operations were accomplished successfully without intraoperative blood transfusion, conversion to thoracotomy, major complication and postoperative 90‐day death. The mean operation time was 220.1 ± 65.6 minutes, median thoracic drainage duration was four days (range: 2–8 days), mean pleural drainage was 1387.5 ± 694.7 mL, and median postoperative hospital stay was seven days (range: 5–18 days). There were three cases (18.8%) of minor complications, including one case of pulmonary air leakage, one case of atrial fibrillation, and one case of poor healing of surgical site. A total of 50% (8/16) of the patients had severe postoperative pain and required additional analgesia. Conclusions For selected patients, simultaneous bilateral pulmonary resection via single‐utility port VATS is a safe and feasible minimally invasive procedure for BMPNs. Adequate postoperative analgesia via a multimodal analgesia strategy should be used to prevent postoperative pain. Key points Significant findings of the study The incidence of major complication after minimally invasive bilateral pulmonary resection is low for patients with good pulmonary function, but there is a relatively high incidence of minor complications and pain at the surgical site. Adequate postoperative analgesia via multimodal analgesia strategy should be used to prevent postoperative pain. What this study adds For the treatment of bilateral multiple pulmonary nodules, simultaneous bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery is safe and feasible for selected patients., Simultaneous bilateral pulmonary resection via single‐utility port video‐assisted thoracoscopic surgery is safe and feasible for the treatment of bilateral multiple pulmonary nodules in selected patients with good pulmonary function.

Inflammatory bowel disease (IBD) is associated with the microbial composition of the gut and its metabolites.

Thymectomy plays an important role in patients with myasthenia gravis (MG) and video-assisted thoracoscopic (VATS) extended thymectomy has been widely used in recent years. The traditional thoracoscopic procedure requires three intercostal incisions. Our study improved the surgical approach and operation method by using single-utility port thoracoscopy. The aim of this study was to evaluate the effect of single-utility port VATS extended thymectomy for MG.A retrospective analysis was performed in 45 patients with MG who underwent single-utility port VATS extended thymectomy in Beijing Hospital from July 2017 to December 2018. The safety and effectiveness of this surgical approach were summarized.All operations were accomplished successfully, without conversion to thoracotomy, requirement of additional incisions or postoperative death. The mean operation time was (141.3±39.2) min; the mean intraoperative blood loss was (64.2±45.5) mL; the median thoracic drainage duration was 3 days (range 2 days to 8 days); the mean pleural drainage was (890.4±439.1) mL, and the median postoperative hospital stay was 6 days (range 3 days to 91 days). There were 13 cases (28.9%) with postoperative complications, including 5 cases (11.1%) with myasthenia crisis, 6 cases (13.3%) with pulmonary complications, 4 cases (8.9%) with poor incision healing, 4 cases (8.9%) with atrial fibrillation, and 1 case (2.2%) with delayed pericardial hemorrhage. The median follow-up time was 18.5 months (range 12.5 months to 29.2 months). According to the effect of 1 year after surgery, 1 case (2.2%) showed pharmacologic remission; 18 cases (40.0%) showed minimal manifestations; 23 cases (51.1%) got improvement; 1 case (2.2%) showed no changs and 2 cases (4.4%) were worse.Single-utility port VATS extended thymectomy is a safe and feasible minimally invasive procedure for MG. During the perioperative period, special attention should be paid to prevent myasthenic crisis, pulmonary complications, and incision complications.【中文题目：单操作孔胸腔镜胸腺扩大切除治疗重症肌无力：附45例报告】 【中文摘要：背景与目的 胸腺切除已成为重症肌无力（myasthenia gravis, MG）治疗的重要组成部分，近年来，经电视胸腔镜（video-assisted thoracoscopic surgery, VATS）胸腺扩大切除得到广泛应用。传统VATS术式多需3个经肋间切口，本研究改良了手术入路和操作方式，现总结单操作孔VATS胸腺扩大切除治疗MG的效果。方法 回顾性分析2017年7月-2018年12月北京医院胸外科应用单操作孔VATS行胸腺扩大切除术的45例MG患者资料，总结其手术安全性和疗效。结果 本组45例均顺利完成胸腺扩大切除，无中转开胸、增加切口和围术期死亡，平均手术时间（141.3±39.2）min，平均术中出血量（64.2±45.5）mL，中位胸腔引流管留置时间3 d，平均胸腔引流量（890.4±439.1）mL，中位术后住院时间6 d。围术期并发症13例（28.9%），其中肌无力危象5例（11.1%），肺部并发症6例（13.3%），切口愈合不良4例（8.9%），房颤4例（8.9%），迟发性心包积血1例（2.2%）。中位随访时间18.5个月，统计术后1年的疗效，药物缓解1例（2.2%），微小症状表现18例（40.0%），改善23例（51.1%），无变化1例（2.2%），加重2例（4.4%）。结论 单操作孔胸腔镜下胸腺扩大切除术治疗MG的手术安全性和疗效良好，围术期应注意预防肌无力危象、肺部并发症和切口并发症。】 【中文关键词：重症肌无力；胸腺扩大切除；电视胸腔镜；单操作孔】.

// Dian Fu 1, * , Ping Li 1, * , Wen Cheng 1 , Feng Tian 2 , Xiaofeng Xu 1 , Xiaoming Yi 1 , Chaopeng Tang 1 , Yongzhong Wang 3 , Quansheng Hu 4 , Zhengyu Zhang 1 1 Department of Urology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China 2 Department of Urology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China 3 Department of Urology, The First People’s Hospital of Huoqiu City, Huoqiu, Anhui, China 4 Department of Urology, Southwest Hospital of the Third Military Medical University, Chongqing, China * These authors contributed equally to this work Correspondence to: Xiaoming Yi, email: yixxmm665@163.com Chaopeng Tang, email: tangchaopeng231@sohu.com Feng Tian, email: tianfeng5573tf@21cn.com Keywords: bladder cancer, vascular endothelial growth factor, single nucleotide polymorphisms, interaction, smoking Received: December 08, 2016 Accepted: January 27, 2017 Published: February 11, 2017 ABSTRACT Aims: To investigate the association of single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) gene polymorphisms, additional gene- gene and gene- smoking interactions with bladder cancer risk. Results: Bladder cancer risk was significantly higher in carriers of the rs699947- A allele within VEGF gene than those with rs699947- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.70 (1.16–2.31), and higher in carriers of the rs833052- A allele of within VEGF gene than those with rs833052- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.65 (1.23–2.12). GMDR analysis indicated a potential interaction between rs2010963 and smoking on bladder cancer risk. Current smokers with rs2010963- GC+CC genotype within VEGF gene have the highest bladder cancer risk, compared to never smokers with rs2010963- GG genotype within VEGF gene, OR (95%CI) = 3.25 (1.71–4.83). Haplotype containing the rs2010963- C and rs833052- A alleles were associated with a statistically increased bladder cancer risk, OR (95%CI) = 2.21 (1.12–3.42). Materials and Methods: Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association of 6 SNPs within VEGF gene, additional gene- gene and gene- smoking interaction with bladder cancer risk. Conclusions: We found that the A allele of rs699947 and the A allele of rs833052 within VEGF gene, interaction between rs2010963 and smoking, haplotype containing the rs2010963- C and rs833052- A alleles were all associated with increased bladder cancer risk.

Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates of Hedera helix (English ivy), have shown promising potential to be used in nanomedicine owing to their excellent aqueous solubility, low intrinsic viscosity, biocompatibility, and biodegradability. In this study, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine are evaluated. Via electrostatic and hydrophobic interactions, pH-responsive nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an entrapment ratio of 77.9 ± 3.9%. While the INPs show minimal cytotoxicity, the formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than free DOX against multiple cancer cell lines, suggesting a synergistic effect is established upon conjugation. The anti-cancer effects of the INP-DOX conjugates are further evaluated via in vivo xenograft assays by subcutaneously implanting DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice treated with the INP-DOX conjugates are significantly less than those of the mice treated with free DOX. In addition, the INPs are further exploited as nano-fillers to develop fibrous scaffolds with collagen, via mimicking the porous matrix where the INPs are embedded under natural condition. Enhanced adhesion of smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are observed in this newly constructed scaffold. Overall, the results obtained from the present study suggest great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein architecture that is amenable for modification according to the functional designs, capable of being developed as versatile nanomaterials for extensive biomedical applications. Statement of Significance Naturally occurring organic nanomaterials have drawn increasing interest for their potential biomedical applications in recent years. In this study, a new type of naturally occurring nanoparticles obtained from the sticky exudates on the adventitious roots of English ivy ( H. helix ), was explored for its potential biomedical application. In particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine were evaluated both in vitro and in vivo . Overall, the results obtained from the present study suggest the great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. This study may open a totally new frontier for exploring the biomedical application of naturally occurring nanomaterials.

SUMMARYToxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains elusive. To explore the role of T. gondii in the development of neural stem cells (NSCs), NSCs were isolated from GD14 embryos of ICR mice and were co-cultured with tachyzoites of T. gondii RH strain. We found that apoptosis levels of the NSCs co-cultured with 1×106 RH tachyzoites for 24 and 48 h significantly increased in a dose-dependent manner, as compared with the control. Western blotting analysis displayed that the protein level of C/EBP homologous protein (CHOP) was up-regulated, and caspase-12 and c-Jun N-terminal kinase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by the T. gondii. The findings here highlight that T. gondii induced apoptosis of the NSCs through the ERS signal pathway via activation of CHOP, caspase-12 and JNK, which may constitute a potential molecular mechanism responsible for the cognitive disturbance in neurological disorders of T. gondii.

Construction of a novel PEGylated bioactive lipids-based micelle system for co-delivery of doxorubicin (DOX) and short chain ceramide (C6-ceramide) to overcome multidrug resistance in leukemia. The PEGylated bioactive lipids-based micelle system was constructed via electrostatic and hydrophobic interactions among DOX, bioactive lipids PazPC and C6-ceramide. The micellar formulation was characterized in terms of size, zeta potential, stability and release behavior, etc., and in vitro cytotoxicity, in vivo antitumor efficacy and the underlying mechanism were further evaluated. This novel micellar system showed small size (~15 nm), high drug encapsulation efficiency (>90%), good stability and endosomal acid-triggered release of DOX. Synergistic cytotoxic effects between DOX and bioactive lipid C6-ceramide in P-gp overexpressing drug resistant leukemia P388/ADR cells were observed. The mechanistic studies demonstrated that modulation of drug efflux system and induction of apoptotic effects by lipids were responsible for the synergistic effects between DOX and C6-ceramide in drug resistant leukemia P388/ADR cells. Using an in-vivo P388/ADR leukemia mouse model, the median survival time of the DOX-loaded PEGylated micelles with PazPC and C6-ceramide as major components was significantly greater than that of free DOX and control group. We developed a novel pH sensitive bioactive lipids-based micellar formulation which could potentially be useful in delivering chemotherapeutic drug DOX and provide a novel strategy to increase the therapeutic index for drug resistant leukemia treatment.

YKL-40 is involved in remodelling and angiogenesis in non-cardiac inflammatory diseases. Aim was to quantitate plasma YKL-40 in patients with ST-elevation myocardial infarction (STEMI) or stable chronic coronary artery disease (CAD), and YKL-40 gene activation in human myocardium.We included 73 patients: I) 20 patients with STEMI; II) 28 patients with stable CAD; III) 15 CAD patients referred for coronary by-pass surgery. YKL-40 mRNA expression was measured in myocardium subtended by stenotic or occluded arteries and areas with no apparent disease; and IV) 10 age-matched healthy controls. Plasma YKL-40 was significantly increased in patients with STEMI (88 microg/l, median) and CAD (66 microg/l) compared to controls (16 microg/l, p0.01 for both). Plasma YKL-40 correlated with CRP at baseline in STEMI (r=0.53, p=0.02) and CAD patients (r=0.41, p=0.031).YKL-40 gene expression was similar in ischemic and non-ischemic myocardium.Plasma YKL-40 was significantly increased in patients with STEMI and stable CAD. Further studies will define the role of YKL-40 as a clinically useful marker for myocardial ischemia, remodelling and maybe prognosis.

Knowledge of the natural course after an ST-elevation myocardial infarction (STEMI) treated according to guidelines is limited because comprehensive serial magnetic resonance imaging (MRI) of systolic left ventricular function, edema, perfusion, and infarct size after STEMI has not been undertaken. The aim of this study was to evaluate effects of therapy for STEMI on left ventricular function and perfusion and to test the hypothesis that myocardial perfusion by MRI predicts recovery of left ventricular function.Cine MRI, edema, first-pass perfusion, and late enhancement imaging were performed in 58 patients at day 2 and at 1 and 6 months after successful primary percutaneous coronary stent intervention for STEMI.Ejection fraction increased 6.3% during the first month (P.001) and 1.9% from 1 to 6 months (P.06), indicating a maximal recovery very early after the infarction. The systolic wall thickening in the infarct area almost doubled (P.001), the perfusion of infarcted myocardium increased approximately 50% (P = .02), and perfusion improved in 72% of patients. Edema decreased with a mean of 2 segments (P.001) during the first month and another 2.5 segments from 1 to 6 months (P.001). Infarct size decreased to 1 month (P = .01) and was unchanged from 1 to 6 months (P = .5). Baseline perfusion did not predict improvement in ejection fraction (r = 0.2, P = .2) but did predict regional systolic function (P = .03).Left ventricular function, perfusion, and infarct mass recovered substantially after STEMI, with the main part of the change within the first month. First-pass perfusion at rest appeared to predict regional ventricular recovery.

Objectives. To investigate the mobilization of non-haematopoietic and haematopoietic cells from the bone marrow induced by intramyocardial VEGF gene therapy and G-CSF treatment alone or in combination in patients with chronic ischemic heart disease (IHD). Secondly, we tested the hypothesis that the quantity of circulating stem cells correlated with improvement in symptoms. Design. We treated I) 16 patients with intramyocardial placebo injections, II) 16 patients with intramyocardial VEGF-A165 gene injections, III) 13 patients with low dose G-CSF, and IV) 16 patients with intramyocardial VEGF-A165 gene followed by high dose G-CSF. Results. Circulating CD34� cells and CD45 � CD34� cells increased by G-CSF in a dose-dependent manner, but did not increase with VEGF gene therapy. The CD45 � /CD34 � cells subgroups increased in both G-CSF treated groups. No association was found between the concentration of mobilized stem cells in the circulation and improvement in symptoms. Conclusions. G-CSF mobilized both haematopoietic and non-haematopoietic cells from the bone marrow in a dose-dependent manner in patients with chronic IHD. However, even high levels of circulating stem cells did not improve symptoms of IHD.

To evaluate the effect of total saponins of Clematis (TSC) on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signal transduction pathway in adjuvant-induced arthritis (AIA) rats and investigate the probable mechanisms.Sixty male SD rats were randomized divided into six groups: normal group, model control group, (50, 100, 200 mg/kg) TSC group, and tripterygium glycosides tablet (10 mg/kg) group (10 rats in each group). Except the normal group, AA models were induced with Freund's complete adjuvant. Twelve days after modeling, corresponding drugs were given to rats by intragastric administration, q.d, for 16 days. Then, the effects of drugs on the body mass and paw swelling of AA rats were observed, and ankle-joint samples were taken to examine the degree of AA by HE staining. Moreover, real-time fluorescent quantitative PCR was performed to detect the expressions of JAK2 and STAT3 mRNA, and Western blotting to determine the expression of p-JAK2, JAK2, p-STAT3, and STAT3 protein.Compared with the model group, TSC not only effectively alleviated the body mass loss and significantly inhibited paw swelling in AA rats, but also significantly inhibited inflammatory cell infiltration, pannus formation and tissue proliferation. Furthermore, TSC treatment obviously decreased mRNA expressions of JAK2 and STAT3 as well as the relative expressions of p-JAK2/JAK2 protein and p-STAT3/STAT3 protein in synovial tissues.TSC can inhibit JAK2/STAT3 signal pathway by decreasing the expressions of JAK2 and STAT3 mRNA and the relative expressions of p-JAK2/JAK2 protein and p-STAT3/STAT3 protein of synovial tissues in AA rats.

To explore the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphism and primary biliary cirrhosis (PBC) in Jiangsu Han population.Peripheral blood samples were taken from 122 patients with PBC hospitalized in third people's hospital of Changzhou in Jiangsu province between June 2011 and July 2013 and 198 randomly matched unrelated healthy donors. KIR was typed by SYBR(R)Green I real-time PCR genotyping assay. Gene and genotype frequencies of KIR were compared between the two groups.The gene frequencies of KIR2DL2 and 2DS2 were significantly lower in the PBC group as compared with those of the control group. KIR2DL2 and 2DS2 were associated with lower risk of PBC. The total 55 KIR genotypes were found in the patients (24 genotypes) and the controls (47 genotypes). The most commonly observed KIR genotype was AA1 , and the next were BX2, BX8, BX4 and BX14 . Only 11 genotypes were observed in five individuals or more, allowing for a meaningful comparison of genotype frequencies between the patients and controls. There was no statistically significant difference in genotype frequencies between the two groups.The absence of KIR2DL2/2DS2 genotype may be associated with protection against PBC in Jiangsu Han population.

Objectives A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. Design, patients and results 29 patients with IHD participated in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were "poor mobilizers" with a maximal increase in CD34+ cells to 5,000±700/mL blood (mean±S.D.) compared to 28,900±5,100/mL blood in "mobilizers". At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in "mobilizers" compared to controls. Myocardial perfusion was unchanged at adenosine stress single photon emission computerized tomography (SPECT) or magnetic resonance images (MRI). Left ventricular ejection fraction decreased from 57% to 52% ( p p =0.07, SPECT) in G-CSF treated, but was unchanged measured with echocardiography. Conclusions Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded.

Sperm quality of the sea urchin, Anthocidaris crassispina, after exposure to environmentally realistic UV-B irradiances, was assessed by changes in sperm motility (measured by the computer-assisted sperm analysis (CASA) system), and related to subsequent fertilization success. Percentage motile sperm of A. crassispina declined significantly after exposure to a UV-B dose of 16.2 kJ m(-2), while sperm motion velocity as measured by curvilinear velocity (VCL), straight line velocity (VSL), and average path velocity (VAP) showed significant reduction after exposure to a UV-B dose of 5.4 kJ m(-2). A parallel study showed that fertilization success was significantly reduced after sperm were exposed to UV-B doses > or = 5.4 kJ m(-2). Notably, the four sperm motility parameters were strongly correlated with fertilization success (P < 0.001), followed the increasing order: VSL (r = 0.8) < % motile sperm (r = 0.804) < VCL (r = 0.912) < VAP (r = 0.928). Fertilization success is best predicted by VAP using the exponential model: y = 8.678 + 90.202/[1 + exp(82.83 - x)/10.27)] (r(2) = 0.95). Thus, impairment of sperm motility of sea urchin, as measured by the CASA method, can be used to predict reproductive success and ecological effects.

The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG), total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), lipoprotein (a) (Lp(a)), blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT), and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P < 0.05). Moreover, we demonstrated that patients' plasma levels of total cholesterol, LDL-C, HDL-C and apoAI were lower at the active phase of the diseases than at the recovering phase, which indicating that acute liver damage could significant influence lipid metabolism in vivo. No pathological changes of blood coagulation status occurred in these patients during the study as all selected patients had moderate hepatitis. It may conclude that examinations of plasma lipid profile could be considered as a clinical index to reflect liver damage in the active phase of hepatitis.

To test the hypothesis that mutations in the vascular endothelial growth factor (VEGF) gene are associated with plasma concentration of VEGF and subsequently the ability to influence coronary collateral arteries in patients with coronary heart disease (CHD).Blood samples from patients with chronic ischemic heart disease (n=53) and acute coronary syndrome (n=61) were analysed. Coronary collaterals were scored from diagnostic biplane coronary angiograms.The plasma concentration of VEGF was increased in patients with acute compared to chronic CHD (p=0.01). The genotype frequencies differed significantly from Hardy-Weinberg equilibrium in three of 15 examined loci. Four new mutations in addition to the already described were identified. The VEGF haplotype did not seem to predict plasma VEGF concentration (p=0.5). There was an association between the genotype in locus VEGF-1154 and coronary collateral size (p=0.03) and a significant association between the VEGF plasma concentration and the collateral size (p=0.03).VEGF plasma concentration seems related to coronary collateral function in patients with CHD. The results did not support the hypothesis that polymorphisms in the untranslated region of the VEGF gene were associated with the concentration of circulating VEGF. Increased understanding of VEGF in the regulation of myocardial collateral flow may lead to new therapies in CHD.

Background: Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial. Methods: Timing of G-CSF treatment was analyzed in the STEMMI MRI subpopulation including 54 patients with STEMI treated with primary percutaneous coronary intervention (PCI) b12 h after symptom onset. Patients were randomized to double blind treatment with GCSF (10 µg/kg/day) or placebo. Treatment was initiated from 17 to 65 h (mean 30) after PCI. Left ventricular ejection fraction (LVEF) was evaluated with MRI. Results: Recovery of LVEF from baseline to 6 months was not associated with time from PCI to G-CSF. An identical improvement in LVEF was found in the placebo group and the G-CSF group (p=0.8). There was no correlation between time from PCI to G-CSF and maximum plasma concentration of CD34+ cells (r=�0.3, p=0.1). Similar results were found from data on recovery of the infarction size and change in the systolic wall thickening. Conclusions: In the time window from 17 to 65 h after STEMI treated with PCI, the timing of G-CSF treatment does not seem to affect the recovery of LVEF. It remains to be determined if very early, or very late G-CSF treatment might be effective. © 2008 Elsevier Ireland Ltd. All rights reserved.

Aims To assess the safety and effects of combined treatment with vascular endothelial growth factor-A165 plasmid (VEGF-A165) and granulocyte- colony stimulating factor (G-CSF) mobilization of bone marrow stem cells in patients with severe chronic ischaemic heart disease (IHD). Methods and results Sixteen patients with severe chronic IHD were treated with intramyocardial injections of VEGF-A165 plasmid followed 1 week later by G-CSF (10 mg/kg/day for 6 days). Two control groups included (i) sixteen patients treated with intramyocardial injections of VEGF-A165 plasmid and (ii) sixteen patients treated with intramyocardial injections of placebo. In the G-CSF group, circulating CD34þ stem cells increased almost 10-fold compared with the control groups (P , 0.0001). After 3 months, there was no improvement in myocardial perfusion at single photon emission computerized tomography in the VEGF-A165 and G-CSF treated group, and clinical symptoms were unchanged. There were no side effects to the gene and G-CSF therapy. Conclusion Intramyocardial VEGF-A165 gene transfer followed by bone marrow stem cell mobilization with G-CSF seemed safe. However, a significant increase in circulating stem cells did not lead to improved myocardial perfusion or clinical effects suggesting a neutral effect of the treatment. To improve homing of stem cells, higher doses of VEGF-A165 and/or use of SDF-1 transfer might be considered.

Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression.Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors.There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium.These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium.

Background— Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction. Methods and Results— Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention P =1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P =0.9) and echocardiography (5.7 versus 3.7; P =0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups. Conclusions— Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group.

Objective: To investigate the spontaneous occurrence of circulating mesenchymal stem cells (MSC) and angiogenic factors in patients with ST elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Design: In 20 patients with STEMI, blood samples were obtained on days 1, 3, 7, 14, 21, and 28 after the acute PCI. Fifteen patients with a normal coronary angiography formed a control group. MSC (CD45−/CD34−), plasma stromal derived factor 1 (SDF-1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2) were measured by multiparametric flow cytometry and enzyme linked immunosorbent assay (ELISA). Results: Circulating CD45−/CD34− cells were significantly decreased on day 7 compared with day 3. Cell counts normalised one month after the acute onset of STEMI. The changes were mainly seen in patients with a large infarction. Plasma SDF-1 increased significantly from day 3 to day 28, and VEGF-A and FGF-2 increased significantly from day 7 to day 28. Conclusions: Spontaneous sequential fluctuations in MSC and the increase in vascular growth factor concentrations after STEMI suggest that the optimal time for additional stem cell therapy is three weeks after a myocardial infarction to obtain the maximum effects by stimulating endogenous growth factors on the delivered stem cells.

Plasma concentrations of endothelin-1 and big-endothelin are increased in heart failure patients. However, the precise contribution of endothelin secretion from the cardiopulmonary system remains unresolved. The aim of this study was to investigate whether the cardiopulmonary system contributes to the circulating endothelin-1 and big-endothelin concentrations in heart failure patients.Blood samples were obtained at right heart catheterization from different cardiovascular regions including the coronary sinus in chronic heart failure patients (n=12) and from age-matched control subjects (n=12).The peripheral plasma concentrations of endothelin-1 were almost 3-fold higher in heart failure patients compared with the control subjects (1.25 pmol/l, 0.30-8.20 pmol/l (median, range) versus 0.46 pmol/l, 0.10-0.88 pmol/l, p0.01). However, the endothelin-1 concentration was approximately 25% lower in plasma samples from the coronary sinus than in plasma from the inferior caval vein (p0.05) in the heart failure patients. There were no differences in big-endothelin concentrations between any of the cardiovascular regions.In heart failure patients, increased plasma concentrations of endothelin-1 and big-endothelin mainly reflect an increased secretion from the peripheral endothelium.

The influence of treatment with granulocyte-colony stimulating factor (G-CSF) on the development of in-stent intimal hyperplasia is not known. We aimed to study this phenomenon in patients who had stents implanted in the course of an acute ST-elevation infarction and successively were treated with G-CSF.We performed angiography and intracoronary ultrasound follow-up after 5 months in 41 consecutive patients in the STEMMI trial, which is a randomized double-blind placebo-controlled study on the effect of G-CSF injections on the myocardial function following acute myocardial infarction in patients treated with primary percutaneous coronary stent implantation. The intracoronary ultrasound images were analyzed by a blinded and independent core laboratory.There were no differences in in-stent neo-intimal hyperplasia determined by intracoronary ultrasound between patients treated with G-CSF compared to patients treated with placebo. Neo-intimal hyperplasia per mm of stent was 1.87 (+/-1.41) and 1.89 (+/-1.39), respectively (p = 0.97). Angiographic in-segment restenosis (50% diameter stenosis) was found in 28% of patients (24% in the G-CSF group and 33% in the placebo group; p = 0.55).G-CSF treatment following coronary stent implantation in primary PCI treated AMI patients does not increase in-stent restenosis excessively and it does not seem warranted to limit further study of effects of G-CSF for that reason.

To investigate the distribution of HBV genotypes in Changzhou area and to clarify the genotype-related difference in the liver function, the level of HBV DNA and the long-term effect of lamivudine in the pathogenicity of HBV.Nested PCR and sequence analysis were conducted in 14 acute hepatitis (AH), 104 chronic hepatitis (CH), and 28 liver cirrhosis or hepatocellular carcinoma (LC/HCC) patients.One hundred and forty six samples were positive for HBV DNA, and 51 samples were classified as genotype B (34.9%), 95 samples were classified as genotype C, serum ALT value was 383.8 +/- 335.7 IU in patients with HBV genotypes B, and 364.3 +/- 333.7 IU in genotypes C, HBV DNA value was 10(7.795 +/- 1.22) copies/ml in genotypes B and 10(7.69 +/0- 1.19) copies/ml in genotypes C, and there were 36 and 64 HBeAg positive cases in patients with genotypes B and C; there were no significant difference on the level of ALT, HBV DNA and the expression of HBeAg (P0.05), but genotype C in LC/HCC was higher than CH (P0.01). Twenty three genotype B and forty five genotype C patients received lamivudine treatment, after 48 weeks, 18 genotype B and 14 genotype C patients had higher ALT or HBV DNA positive.These results indicate that genotype B and C existing Changzhou area; genotype C is associated with the development of severe liver disease and better therapeutic effect could be obtained in the patients with genotype C.

Angiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease.Fifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects.Plasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34-/CD45- cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p0.005-0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p=0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea.Plasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden.