Search

OBJECTIVES According to retrospective studies, oesophageal carcinoma is the second deadliest gastrointestinal cancer after gastric cancer. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve the inflammatory response of patients undergoing oesophagectomy; however, conclusions across studies remain unclear. We aimed to evaluate the effect of EIN on the clinical and immunological outcomes of patients undergoing oesophagectomy. METHODS Four electronic databases (MEDLINE, Embase, Web of Science and Cochrane Library) were used to search articles in peer-reviewed, English-language journals. The mean difference, relative risk or standard mean difference with 95% confidence interval were calculated. Heterogeneity was assessed by the Cochran’s Q test and I2 statistic combined with the corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS Six articles were finally included, with a total of 320 patients with oesophageal cancer. The meta-analysis results showed that EIN did not improve clinical outcomes (such as infectious complications, pneumonia, surgical site infection, anastomotic leak and postoperative hospital stay) or immune indices [referring to C-reactive protein, interleukin (IL)-6, IL-8, tumour necrosis factor-α]. Descriptive analysis suggested that EIN also increased the serum concentrations of IgG and the percentage of the B-cell fraction. Thus, its impact on IL-8 and IL-6 remains inconsistent. CONCLUSIONS The early-stage impact of EIN on immunological status in patients undergoing oesophagectomy is still unclear. According to the results of this meta-analysis, whether EIN could improve the clinical outcomes or biological status after oesophagectomy compared to standard enteral nutrition is uncertain. Since the impact of EIN is unclear, current guidelines that strongly advise the use of EIN should be changed, as the utility of EIN is very uncertain. More appropriately powered clinical studies are warranted to confirm its effectiveness.

Purpose The goal of present study is to document our single-center experience with chimney technique for aortic arch diseases. Patients and methods From August 2012 to October 2017, 226 patients (mean age 54±12 years; 197 men) with aortic arch diseases underwent thoracic endovascular aortic repair combined with chimney stents. The aortic stent-grafts were deployed in zone 0 (n=22), zone 1 (n=13), or zone 2 (n=191). Results The technical success rate was 84% (189/226) and immediate type Ia endoleak (ELIa) happened in 37 (16%) patients. The 30-day mortality and morbidity rates were 2% (4/226) and 4% (8/226), respectively. Major adverse events include four major strokes, three spinal cord ischemia and one aortic rupture in the early-term. The clinical and imaging follow-up rates were 98% (218/222) and 78% (173/222), respectively. The average lengths of clinical and imaging follow-up were 22±16 months and 20±15 months, respectively. Chimney stent obstructions in left subclavian arteries were recorded in six (3%) patients. During follow-up, five patients died (2%) and two major strokes occurred (1%). One patient (0.5%) underwent reintervention. Conclusion The current study documented that the chimney technique is effective and safe for treating aortic arch diseases in different aortic zones. Cautions are needed to assess the permanency of chimney stent and to reduce the immediate ELIa rate.

Purpose Eukaryotic initiation factor 2α (eIF2α) plays important roles in the proliferation and survival of pulmonary artery smooth muscle cells (PASMCs) in animal hypoxia-induced pulmonary hypertension models. However, the underlying mechanism remains unknown at large. Autophagy has been reported to play a key role in the vascular remodeling in pulmonary arterial hypertension (PAH). The purposes of this study are to determine the functions of eIF2α and autophagy in the vascular remodeling of the monocrotaline-induced PAH rats and to clarify the correlation between eIF2α and autophagy. Methods We established a rat model of monocrotaline-induced PAH, and we established a cell model of platelet derived growth factor (PDGF)-induced PASMCs proliferation. The vascular morphology and the expression of eIF2α, LC3B, and p62 were assessed in the pulmonary arterial tissue of Sprague-Dawleyrats and PDGF-induced PASMCs. Results Autophagy was significantly active in monocrotaline model group (MCT)-induced PAH rats, which obviously promotes vascular remodeling in MCT-induced PAH rats. Furthermore, the proliferation of PASMCs was induced by PDGF in vitro. The expression of LC3B, eIF2α was increased in the PDGF-induced PASMCs proliferation, and the expression of p62 was reduced in the PDGF-induced PASMCs proliferation. Moreover, eIF2α siRNA downregulated the expression of eIF2α and LC3B, and upregulated the expression of p62 in PDGF-induced PASMCs proliferation. eIF2α siRNA inhibited the PDGF-induced PASMCs proliferation. Finally, chloroquine can upregulate the protein expression of LC3B and p62, it also can inhibit proliferation in PDGF-induced PASMCs. Conclusion Based on these observations, we conclude that eIF2α promotes the proliferation of PASMCs and vascular remodeling in monocrotaline-induced PAH rats through accelerating autophagy pathway.

OBJECTIVES Pulmonary sequestration is a rare congenital pulmonary malformation. The aim of this study was to explore the effect of different therapeutic strategies on the clinical outcome of asymptomatic intralobar pulmonary sequestration. METHODS We retrospectively reviewed the clinical data of 37 patients diagnosed with intralobar sequestration. All the patients were asymptomatic. Seventeen patients underwent video-assisted thoracoscopic surgery (VATS) once diagnosed and 20 patients chose to undergo observation. Of these 20 patients, 16 patients developed symptoms during the observation period and also underwent VATS; 4 patients never showed symptoms and did not have surgery. The 33 patients who had VATS were divided into 2 groups: group 1, patients who underwent VATS once diagnosed; group 2, patients who underwent VATS once symptoms appeared. Postoperative data and respiratory function data were compared between the 2 groups. RESULTS Twenty of the patients were men and 17 were women (mean age 37.05 ± 7.89 years). Results of a comparative analysis of the 2 groups indicated that patients in group 1 had better values for median estimated blood loss, median duration of chest tube insertion, postoperative hospital stay and postoperative hospital stay than those in group 2. Postoperative complications were reported in 1 patient in group 1 and in 3 patients in group 2. Meanwhile, the loss of lung function between group 1 and group 2 was statistically significant, which also suggested that patients benefited from surgery once diagnosed. CONCLUSIONS For asymptomatic intralobar sequestration, VATS could be effective and safe. The surgical intervention should be performed once the condition is diagnosed to avoid manifestations occurring and to preserve patients’ quality of life.

Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665–miR98–AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Nevertheless, the detailed molecular mechanisms of the progression of LUAD remain largely unknown. The present bioinformatics analysis reported that FAM83A and FAM83A-AS1 were upregulated in LUAD tissues and associated with prognosis in patients with LUAD. The purpose of the current study was to investigate the role of FAM83A and its antisense long non-coding (lnc)RNA FAM83A-AS1 in LUAD. Gene Expression Profiling Interactive Analysis was used to screen for potential oncogenes in LUAD and to analyze the clinical significance of FAM83A and FAM83A-AS1. Small interfering RNAs were constructed and transfected into LUAD cells to knock down the expression of FAM83A and FAM83A-AS1. EdU, Cell Counting Kit-8, Transwell and Matrigel assays were performed to detect the proliferation, migration and invasion of LUAD cells. The interaction between FAM83A-AS1, microRNA (miR)-495-3p and FAM83A was explored using a luciferase reporter assay. FAM83A and FAM83A-AS1 were both overexpressed in LUAD tissues compared with adjacent normal tissues. High expression of FAM83A and FAM83A-AS1 predicted worse survival and more advanced clinical stage. Knockdown of FAM83A or FAM83A-AS1 could inhibit the proliferation, migration and invasion of LUAD cells. Moreover, lncRNA FAM83A-AS1 regulated the expression of FAM83A by functioning as competing endogenous RNA for miR-495-3p. These results implicated that FAM83A and FAM83A-AS1 both played oncogenic roles in LUAD and FAM83A-AS1 could regulate the expression of FAM83A by sponging miR-495-3p. The study revealed a novel regulatory mechanism of tumor development in LUAD and FAM83A and FAM83A-AS1 may be novel biomarkers and therapeutic targets for LUAD.

Significance: Perivascular adipose tissue (PVAT), which is present surrounding most blood vessels, from the aorta to the microvasculature of the dermis, is mainly composed of fat cells, fibroblasts, stem cells, mast cells, and nerve cells. Although the PVAT is objectively present, its physiological and pathological significance has long been ignored. Recent Advances: PVAT was considered as a supporting component of blood vessels and a protective cushion to the vessel wall from the neighboring tissues during relaxation and contraction. Nonetheless, further extensive research found that PVAT actively regulates blood vessel tone through PVAT-derived vasoactive factors, including both relaxing and contracting factors. In addition, PVAT contributes to atherosclerosis through paracrine secretion of a large number of bioactive factors such as adipokines and cytokines. Thereby, PVAT regulates the functions of blood vessels through various mechanisms operating directly on PVAT or on the underlying vessel layers, including vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Critical Issues: PVAT is a unique adipose tissue that plays an essential role in maintaining the vascular structure and regulating vascular function and homeostasis. This review focuses on recent updates on the various PVAT roles in hypertension and atherosclerosis. Future Directions: Future studies should further investigate the actual contribution of alterations in PVAT metabolism to the overall systemic outcomes of cardiovascular disease, which remains largely unknown. In addition, the messengers and underlying mechanisms responsible for the crosstalk between PVAT and ECs and VSMCs in the vascular wall should be systematically addressed, as well as the contributions of PVAT aging to vascular dysfunction.

Angiogenesis is a core hallmark of advanced cancers, especially in lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of lncRNAs in tumor angiogenesis remain largely unknown. Here we found that linc00665 depletion could markedly depressed proliferation and capillary tube formation of HUVECs in vitro. Mechanistically, linc00665 directly interacted with YB-1 protein, enhanced its stability through inhibiting ubiquitination-dependent proteolysis and stimulated its nuclear translocation in LUAD cells. The accumulated nuclear YB-1 activated expression of ANGPT4, ANGPTL3 and VEGFA by binding to their promoters, contributing to tumor-related angiogenesis in vitro and in vivo. Collectively, we conclude that linc00665 induces tumor-related angiogenesis in LUAD by directly interacting with YB-1 and activating YB-1-ANGPT4/ANGPTL3/VEGFA axis, which provides promising anti-angiogenic targets for cancer therapy.

Objective To evaluate the safety of early oral feeding in patients with type II diabetes after radical resection of esophageal carcinoma. Methods The clinical data of 121 patients with type II diabetes who underwent radical resection of esophageal carcinoma in the department of cardiothoracic surgery of Jinling Hospital from January 2016 to December 2018 were retrospectively analyzed. According to the median time (7 days) of the first oral feeding after surgery, the patients were divided into early oral feeding group (EOF, feeding within 7 days after surgery, 67 cases) and late oral feeding group (LOF, feeding after 7 days, 54 cases). Postoperative blood glucose level, incidence of complications, nutritional and immune indexes, inflammatory indexes, normalized T12-SMA (the postoperative/preoperative ratio of vertical spinal muscle cross-sectional area at the 12th thoracic vertebra level) and QLQ-C30 (Quality Of Life Questionnaire) scores were recorded and compared in the two groups. Results There was no statistical difference in preoperative nutritional index and postoperative complication rates between the EOF and LOF group (p > 0.05). The postoperative nutritional index (ALB, PA, TRF, Hb) and immune index (IgA, IgG, IgM) of the EOF group were higher than those of the LOF group (p p p Conclusions Early oral feeding is safe and feasible for patients with type II diabetes after radical resection of esophageal cancer, and it can improve short-term nutritional status and postoperative life quality of the patients.

Perivascular adipose tissue (PVAT), the adipose tissue that surrounds most of the vasculature, has emerged as an active component of the blood vessel wall regulating vascular homeostasis and affecting the pathogenesis of atherosclerosis. Although PVAT characteristics resemble both brown and white adipose tissues, recent evidence suggests that PVAT develops from its own distinct precursors implying a closer link between PVAT and vascular system. Under physiological conditions, PVAT has potent anti-atherogenic properties mediated by its ability to secrete various biologically active factors that induce non-shivering thermogenesis and metabolize fatty acids. In contrast, under pathological conditions (mainly obesity), PVAT becomes dysfunctional, loses its thermogenic capacity and secretes pro-inflammatory adipokines that induce endothelial dysfunction and infiltration of inflammatory cells, promoting atherosclerosis development. Since PVAT plays crucial roles in regulating key steps of atherosclerosis development, it may constitute a novel therapeutic target for the prevention and treatment of atherosclerosis. Here, we review the current literature regarding the roles of PVAT in the pathogenesis of atherosclerosis.

Background: The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation. Methods: Using unique brown adipocyte–specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice. Results: We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte–selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor–dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT. Conclusions: These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.

Objective: To investigate the risk factors for neurogenic pulmonary edema (NPE) in patients with severe hand, foot, and mouth disease (HFMD) and to provide evidence for the prevention and treatment of NPE. Methods: Several databases were searched (from inception to 2017) to identify caseâcontrol studies on risk factors for NPE among patients with severe HFMD. Data were analyzed via meta-analysis. The combined odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-effects and random-effects models, and a sensitivity analysis and evaluation of publication bias was also performed. Results: A total of 14 studies involving 557 cases (severe HFMD with NPE) and 1450 controls (severe HFMD) were included. Results for the categorical variables were as follows: hyperglycemia (OR 10.25, 95% CI 4.82â21.76), tachycardia (OR 6.21, 95% CI 3.02â12.75), hypertension (OR 3.79, 95% CI 2.90â4.95), respiratory rhythm abnormality (OR 7.86, 95% CI 2.46â25.12), drowsiness (OR 8.11, 95% CI 4.26â15.44), vomiting (OR 8.96, 95% CI 3.83â20.96), limb tremors (OR 8.96, 95% CI 3.83â20.96), atypical rash (OR 4.27, 95% CI 2.83â6.45). No significant publication bias was found for the different factors. Conclusions: Drowsiness ranks first among risk factors for NPE in children with severe HFMD, followed by vomiting, tachycardia, hypertension, breathing rhythm changes, limb tremors, atypical rash, and hyperglycemia. Keywords: Severe hand, foot, and mouth disease, Neurogenic pulmonary edema, Caseâcontrol study, Meta-analysis, Risk factors

Aim The current study aimed to examine miR‐145's contribution to thoracic aortic dissection (AD) development by modulating the biological functions of vascular smooth muscle cells (VSMCs). Methods The concentration of circulating miR‐145 was determined in patients with AD and healthy controls using quantitative polymerase chain reaction (qPCR). Aortic specimens were obtained from both individuals with Stanford type A AD undergoing surgical treatment and deceased organ donors (serving as controls) whose causes of death were nonvascular diseases. Then, qPCR and fluorescence in situ hybridization were applied to assess miR‐145 amounts and location, respectively. Furthermore, qPCR and immunoblot were employed to determine SMAD3 (the target gene of miR‐145, involved in the TGF‐β pathway) amounts at the gene and protein levels, respectively. Moreover, in vitro transfection of VSMCs with miR‐145 mimics or inhibitors was conducted. Finally, the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, Transwell assay and flow cytometry were employed for detecting VSMC proliferation, migration, and apoptosis, respectively. Results The amounts of miR‐145 in plasma and aortic specimens were markedly reduced in the AD group in comparison with control values (P

SUMMARYThe aims of this pilot study are to evaluate the feasibility, safety, and effectiveness of conducting an enhanced nutritional support pathway including extended preoperative nutritional support and one month home enteral nutrition (HEN) for patients who underwent enhanced recovery after esophagectomy. We implemented extended preoperative nutritional support and one month HEN after discharge for patients randomized into an enhanced nutrition group and implemented standard nutritional support for patients randomized into a conventional nutrition group. Except the nutritional support program, both group patients underwent the same standardized enhanced recovery after surgery programs of esophagectomy based on published guidelines. Patients were assessed at preoperative day, postoperative day 7 (POD7), and POD30 for perioperative outcomes and nutritional status. To facilitate the determination of an effect size for subsequent appropriately powered randomized clinical trials and assess the effectiveness, the primary outcome we chose was the weight change before and after esophagectomy. Other outcomes including body mass index (BMI), lean body mass (LBM), appendicular skeletal muscle mass index (ASMI), nutrition-related complications, and quality of life (QoL) were also analyzed. The intention-to-treat analysis of the 50 randomized patients showed that there was no significant difference in baseline characteristics. The weight (−2.03 ± 2.28 kg vs. −4.05 ± 3.13 kg, P = 0.012), BMI (−0.73 ± 0.79 kg/m2 vs. −1.48 ± 1.11 kg/m2, P = 0.008), and ASMI (−1.10 ± 0.37 kg/m2 vs. −1.60 ± 0.66 kg/m2, P = 0.010) loss of patients in the enhanced nutrition group were obviously decreased compared to the conventional nutrition group at POD30. In particular, LBM (48.90 ± 9.69 kg vs. 41.96 ± 9.37 kg, p = 0.031) and ASMI (7.56 ± 1.07 kg/m2 vs. 6.50 ± 0.97 kg/m2, P = 0.003) in the enhanced nutrition group were significantly higher compared to the conventional nutrition group at POD30, despite no significant change between pre- and postoperation. In addition, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scores revealed that enhanced nutritional support improved the QoL of patients in physical function (75.13 ± 9.72 vs. 68.33 ± 7.68, P = 0.009) and fatigue symptom (42.27 ± 9.93 vs. 49.07 ± 11.33, P = 0.028) compared to conventional nutritional support. This pilot study demonstrated that an enhanced nutritional support pathway including extended preoperative nutritional support and HEN was feasible, safe, and might be beneficial to patients who underwent enhanced recovery after esophagectomy. An appropriately powered trial is warranted to confirm the efficacy of this approach.

Canhua Jiang,1 Shufang Jin,1 Zhisheng Jiang,1 Jie Wang2 1Department of Oral and Maxillofacial Surgery, Xiangya Hospital, 2Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Objective: To investigate the possible mechanisms and effects of silibinin (SIL) on the proliferation and lung metastasis of human lung high metastasis cell line of salivary gland adenoid cystic carcinoma (ACC-M).Methods: A methyl thiazolyl tetrazolium assay was performed to detect the inhibitory effects of SIL on the proliferation of ACC-M cells in vitro. Fluorescence microscopy and transmission electron microscopy were used to observe the autophagic process. Western blot was performed to detect the expression of microtube-related protein 1 light-chain 3 (LC3). An experimental adenoid cystic carcinoma (ACC) lung metastasis model was established in nude mice to detect the impacts of SIL on lung weight and lung cancer nodules. Immunohistochemistry was used to detect the expressions of LC3 in human ACC samples and normal salivary gland tissue samples.Results: SIL inhibited the proliferation of ACC-M cells in a dose- and time-dependent manner, and inductively increased the autophagic bodies in ACC-M cells. Furthermore, SIL could increase the expression of LC3 in ACC-M cells and promote the conversion of LC3-I into LC3-II in a dose- and time-dependent manner. In the ACC lung metastasis model, the lung weight and left and right lung nodules in the SIL-treated group were significantly less than those in the control group (P

BACKGROUND This study aimed to use bioinformatics analysis to compare data from tissue microarrays from patients with lung adenocarcinoma (LUAD) and normal lung tissue, and human lung adenocarcinoma cells with normal lung epithelial cells in vitro to investigate the role of synaptotagmin 12 (SYT12) gene expression in LUAD. MATERIAL AND METHODS Human lung adenocarcinoma cell lines (A549, SPC-A-1, H1299, H1975, and PC9) and the normal HBE cell line were compared, and tumor xenografts were developed in mice. The Cancer Genome Atlas (TCGA) tissue microarray data were used to compare SYT12 expression and overall survival (OS). The in vivo and in vitro effects of down-regulation and upregulation of SYT12 were studied using short-interfering RNA (si-RNA) and overexpression plasmids, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and Western blot investigated the molecular mechanisms of SYT12 expression in LUAD. RESULTS SYT12 expression was increased in tissues from patients with LUAD from TCGA and was associated with advanced tumor stage and reduced prognosis. Knockdown of SYT12 suppressed the proliferation and migration of LUAD cells, and upregulation of SYT12 increased the proliferation and migration of LUAD cells in vitro. Phosphorylation of PIK3R3 activated the PI3K/AKT/mTOR pathway. In the mouse xenograft model, expression of SYT12 increased the volume and weight of the xenograft tumors. CONCLUSIONS Bioinformatics analysis, human LUAD cells, and mouse xenograft studies showed that SYT12 acted as a possible oncogene by phosphorylation of PIK3R3 to activate the PI3K/AKT/mTOR signaling pathway.

Bone marrow-derived mesenchymal stem cells (BMSCs) are a population of multipotent progenitors that have the capacity of proliferation and differentiation into mesenchymal lineage cells. The regulatory peptide apelin is the endogenous ligand for the G protein-coupled receptor APJ. Apelin, which can enhance BMSC proliferation, has mitogenic effects on a wide variety of cell types. We hypothesized that the increased apelin/APJ might be involved in the occurrence and development of hypoxia-induced BMSC proliferation. BMSCs from the bone marrow of 8- to 10-week-old C57BL/6J mice were cultured under either normoxia (21% oxygen) or hypoxia (1% oxygen) condition. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-bromo-2'-deoxyuridine assay. Expressions of hypoxia-inducible factor (HIF)-1α, apelin, APJ, Beclin-1, and LC3II/LC3I were detected by western blot analysis. Results suggested that hypoxia enhanced the proliferation of BMSC in a time-dependent manner. The expressions of HIF-1α, apelin, APJ, Beclin-1, and LC3II/LC3I were increased in BMSCs induced by hypoxia. Small interfering RNA (siRNA)-HIF-1α that inhibited the hypoxia-induced expressions of apelin, APJ, Beclin-1, and LC3II/LC3I prevented hypoxia-induced BMSC proliferation. siRNA-APJ that inhibited the hypoxia-induced expressions of Beclin-1 and LC3II/LC3I reversed hypoxia-induced BMSC proliferation. siRNA-Beclin-1 also abolished hypoxia-induced cell proliferation. These data suggested that the apelin/APJ/autophagy signaling pathway might be involved in hypoxia-induced BMSC proliferation.

Aim: Previous studies have demonstrated that the dysregulated-secretion of adipokines by adipocytes may contribute to obesity-associated atherosclerosis (As) and high density lipoprotein (HDL) may protect against atherogenesis through multiple pathways. This study was to explore the effect of HDL on the oxLDL uptake in inflammatory adipocytes stimulated by endotoxin lipopolysaccharide (LPS) and the possible mechanism. Methods and Results: 3T3-L1 adipocytes were cultured and induced to differentiation and maturation. Acute inflammation in adipocytes was induced by LPS (100 ng/ml) for 6 hours. The adipocytes were pretreated with HDL in various concentrations (10, 50, 100 μg/ml) for 16 hours or with specific PPARγ antagonist (GW9662, 10 μM) or agonist (Rosiglitazone, 10 μM) for 30 min before administration of LPS. The results showed that LPS significantly increased the release of inflammation-related adipokines, such as monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-8 and IL-6, while decreasing the release of leptin and adiponectin. Meanwhile, LPS reduced the uptake and degradation of 125 I-oxLDL, and down-regulated the expression of PPARγ and CD36. Pretreatment with HDL dose-dependently affected the release of IL-8 and IL-6 and the reduced uptake and degradation of oxLDL of adipocytes stimulated by LPS, accompanied with marked upregulation of PPARγ and CD36 expression. Pretreatment with GW9662 markedly inhibited the upregulation of CD36 expression mediated by HDL (100 μg/ml), while the effects of Rosiglitazone were opposite to GW9662. Conclusions: HDL may increase oxLDL uptake of inflammatory adipocytes stimulated by LPS via upregulation of PPARγ/CD36 pathway, which may be a new mechanism of anti-atherosclerosis mediated by HDL.

Background: Perivascular adipose tissue (PVAT), which surrounds most vessels, is de facto a distinct functional vascular layer actively contributing to vascular function and dysfunction. PVAT contributes to aortic remodeling by producing and releasing a large number of undetermined or less characterized factors that could target endothelial cells and vascular smooth muscle cells, and herein contribute to the maintenance of vessel homeostasis. Loss of PVAT in mice enhances atherosclerosis, but a causal relationship between PVAT and atherosclerosis and the possible underlying mechanisms remain to be addressed. The CDGSH iron sulfur domain 1 protein (referred to as mitoNEET), a mitochondrial outer membrane protein, regulates oxidative capacity and adipose tissue browning. The roles of mitoNEET in PVAT, especially in the development of atherosclerosis, are unknown. Methods: The brown adipocyte-specific mitoNEET transgenic mice were subjected to cold environmental stimulus. The metabolic rates and PVAT-dependent thermogenesis were investigated. Additionally, the brown adipocyte-specific mitoNEET transgenic mice were cross-bred with ApoE knockout mice. The ensuing mice were subsequently subjected to cold environmental stimulus and high cholesterol diet challenge for 3 months. The development of atherosclerosis was investigated. Results: Our data show that mitoNEET mRNA was downregulated in PVAT of both peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)- and beta (Pgc1β)-knockout mice which are sensitive to cold. MitoNEET expression was higher in PVAT of wild type mice and increased upon cold stimulus. Transgenic mice with overexpression of mitoNEET in PVAT were cold resistant, and showed increased expression of thermogenic genes. ApoE knockout mice with mitoNEET overexpression in PVAT showed significant downregulation of inflammatory genes and showed reduced atherosclerosis development upon high fat diet feeding when kept in a 16°C environment. Conclusion: mitoNEET in PVAT is associated with PVAT-dependent thermogenesis and prevents atherosclerosis development. The results of this study provide new insights on PVAT and mitoNEET biology and atherosclerosis in cardiovascular diseases.

Background A phase I study to assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and antitumor activity of vorinostat in combination with bortezomib in patients with advanced solid tumors. Methods Patients received vorinostat orally once daily on days 1–14 and bortezomib intravenously on days 1, 4, 8 and 11 of a 21-day cycle. Starting dose (level 1) was vorinostat (400 mg) and bortezomib (0.7 mg/m2). Bortezomib dosing was increased using a standard phase I dose-escalation schema. PKs were evaluated during cycle 1. Results Twenty-three patients received 57 cycles of treatment on four dose levels ranging from bortezomib 0.7 mg/m2 to 1.5 mg/m2. The MTD was established at vorinostat 400 mg daily and bortezomib 1.3 mg/m2. DLTs consisted of grade 3 fatigue in three patients (1 mg/m2,1.3 mg/m2 and 1.5 mg/m2) and grade 3 hyponatremia in one patient (1.5 mg/m2). The most common grade 1/2 toxicities included nausea (60.9 %), fatigue (34.8 %), diaphoresis (34.8 %), anorexia (30.4 %) and constipation (26.1 %). Objective partial responses were observed in one patient with NSCLC and in one patient with treatment-refractory soft tissue sarcoma. Bortezomib did not affect the PKs of vorinostat; however, the Cmax and AUC of the acid metabolite were significantly increased on day 2 compared with day 1. Conclusions This combination was generally well-tolerated at doses that achieved clinical benefit. The MTD was established at vorinostat 400 mg daily × 14 days and bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle.

Background & Aims The rs58542926 C>T variant of the transmembrane 6 superfamily member 2 gene (TM6SF2), encoding an E167K amino acid substitution, has been correlated with reduced total cholesterol (TC) and cardiovascular disease. However, little is known about the role of TM6SF2 in metabolism. We investigated the long-term effects of altered TM6SF2 levels in cholesterol metabolism. Methods C57BL/6 mice (controls), mice that expressed TM6SF2 specifically in the liver, and mice with CRISPR/Cas9-mediated knockout of Tm6sf2 were fed chow or high-fat diets. Blood samples were collected from all mice and plasma levels of TC, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol, and triglycerides were measured. Liver tissues were collected and analyzed by histology, real-time polymerase chain reaction, and immunoblot assays. Adenovirus vectors were used to express transgenes in cultured Hep3B hepatocytes. Results Liver-specific expression of TM6SF2 increased plasma levels of TC and LDL-c, compared with controls, and altered liver expression of genes that regulate cholesterol metabolism. Tm6sf2-knockout mice had decreased plasma levels of TC and LDL-c, compared with controls, and consistent changes in expression of genes that regulate cholesterol metabolism. Expression of TM6SF2 promoted cholesterol biosynthesis in hepatocytes. Conclusions TM6SF2 regulates cholesterol metabolism in mice and might be a therapeutic target for cardiovascular disease.

To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin.Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment.Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer.Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

An amino-derivative of parathion was prepared and conjugated to human serum albumin (HSA) and bovine thyroglobulin (BTG) via diazonium condensation. Spleen cells producing high titer antibody were removed and fused with myeloma cells of SP2/0 origin. Using a conventional immunization protocol, we generated nine stable murine monoclonal antibodies (MAbs) producing cell lines to parathion. After four successive limiting dilutions, antibodies produced by nine clones had high affinities, ranging from 10(9) to 10(12) M(-1). These clones were found to be of IgG class and IgM class with k light chain. Subclass determination showed that the clones produced IgG(1), IgG(2a), IgG(2b), and IgM types of antibody. One clone (2H(9)) was used to establish the calibration curve with a sensitivity of 26 ng/mL, a practical working range of 46.8-6000 ng/mL parathion.

Pannexin-1, Pannexin-2, and Pannexin-3 are three members of the Pannexin family of channel-forming glycoprotein. Their primary function is defined by their ability to form single-membrane channels. Pannexin-1 ubiquitously exists in many cells and organs throughout the body and is specially distributed in the circulatory system, while the expressions of Pannexin-2 and Pannexin-3 are mostly restricted to organs and tissues. Pannexin-1 oligomers have been shown to be functional single membrane channels that connect intracellular and extracellular compartments and are not intercellular channels in appositional membranes. The physiological functions of Pannexin-1 are to link to the adenosine triphosphate efflux that acts as a paracrine signal, and regulate cellular inflammasomes in a variety of cell types under physiological and pathophysiological conditions. However, there are still many functions to be explored. This review summarizes recent reports and discusses the role of Pannexin-1 in cardiovascular diseases, including ischemia, arrhythmia, cardiac fibrosis, and hypertension. Pannexin-1 has been suggested as an exciting, clinically relevant target in cardiovascular diseases.

Five insect growth regulators (IGRs) with juvenile hormone (JH) activity including fenoxy-carb, methoprene, NC-170, NC-184 and NC-196 were selected to study on the relationship between IGRs and feeding behaviour of the fourth instar larvae of Calospilos suspecta (Warren) and the fifth instar larvae of Ostrinia furnacalis Guenee, by topical and dietary applications as well as “diet column” methods. The results indicated that the antifeeding indices of methoprene, fenoxycarb, NC-170, NC-184, NC-196 and toosendanin against the fifth instar larvae of Ostrinia furnacalis in no-choice test were -37. 7, 14. 6, -12. 3, 10. 9, 14. 7 and 62. 2% respectively. Methoprene could stimulate the two species of insects to feed, whereas fenoxycarb had some antifeeding activity, and the effects of all the tested chemicals were different. Therefore, disturbances of IGRs with JH activity on insect feeding behavioural response may be one of the mechanisms of action not to be ignored. Moreover, by comparing “diet column” method with “faeces weight” method, it was suggested that the two methods might be applied in bioassay of antifeeding behaviour.

Purpose The stability of prepared infusions of the tumor necrosis factor (TNF)-α agent infliximab after storage for up to two weeks was investigated. Methods To determine the feasibility of liberalized expiration dating of infliximab (current recommendations call for the infusion of prepared doses within three hours), the stability of diluted infliximab stored in polyvinyl chloride (PVC) bags at 4 °C for up to 14 days was evaluated. A known quantity of TNF-α was combined with infliximab test samples in PVC bags for one hour; immediately after the reaction period and after 7 and 14 days of storage, the residual amount of TNF-α (an indirect measure of the drug’s biological activity) was analyzed via a validated enzyme-linked immunosorbent assay (ELISA). Results The mean ± S.D. amount of TNF-α consumed by infliximab was calculated to be 24.5 ± 5.6 pg/mL at baseline, 29.0 ± 4.4 pg/mL at 7 days, and 24.8 ± 17.3 pg/mL at 14 days. At all evaluated time points, ELISA results indicated that 19–24% of the original TNF-α had been consumed by infliximab (mean ± S.D. consumption: 19.6% ± 4.5% at baseline, 23.2% ± 3.5% at 7 days, and 19.8% ± 13.8% at 14 days). Conclusion Infliximab, when prepared at a concentration of 400 μg/mL in 0.9% sodium chloride injection, incurred no loss of biological activity when stored for up to 14 days at 4 °C in PVC bags. Changing infliximab preparation practices may improve clinic efficiency by reducing patient dissatisfaction with long wait times for infusions and avoiding costly waste.

Gemcitabine is an effective chemotherapy against non-small cell lung cancer (NSCLC). However, resistance to gemcitabine reduces its efficacy. We have isolated gemcitabine-resistant human non-small cell lung cancer A549 cells, termed A549/GR cells. A549/GR cells were resistant to gemcitabine as well as paclitaxel and docetaxel but not carboplatin and irinotecan. The expression level of multidrug resistance protein 7 (MRP7) in A549/GR cells was higher than that in A549 cells, and the inhibitor of MRP7 by cepharanthine increased the sensitivity to gemcitabine in A549/GR cells. These findings indicate that cepharanthine reversed gemcitabine resistance. To determine predictive molecular markers of gemcitabine resistance for more effective treatment of these tumors, we performed PCR array. We identified that CDKN1A/p21, CYP3A5, microsomal epoxide hyrolase 1 (EPHX1) and ABCC6 (MRP6) were up-regulated >5-fold in A549/GR cells. Gemcitabine also induced the expression of p21 and CYP3A5 in A549 cells. A better understanding of the characterization and mechanism of the resistance to gemcitabine in A549/GR cells may help identify agents that reverse clinical gemcitabine resistance in NSCLC.

Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an effective therapy for non-small cell lung cancer (NSCLC). However, resistance to erlotinib reduces its efficacy. To investigate the basis of erlotinib resistance, we isolated erlotinib-resistant human NSCLC A549 cells, termed A549/ER cells. The A549/ER cells were found to be resistant to erlotinib, as well as paclitaxel and gemcitabine. We then performed a PCR array to investigate the resistance to erlotinib in A549/ER cells. EGFR expression in A549/ER cells was decreased compared to A549 cells. The expression of fibroblast growth factor 2 (FGF2) and p21 in A549/ER was increased when compared to A549 cells. Our results suggest that the down-regulation of EGFR and up-regulation of FGF2 is related to resistance to erlotinib in A549/ER cells.

Irinotecan (CTP-11) is a topoisomerase I inhibitor used in the treatment of colorectal cancer and non-small cell lung cancer (NSCLC). Despite an initial response to therapy, resistance to irinotecan reduces its efficacy. We isolated irinotecan-resistant human NSCLC A549 cells, termed A549/CTP-11R cells. A549/CTP-11R cells were resistant to irinotecan, as well as paclitaxel, gemcitabine and carboplatin. Curcumin, a nuclear factor-κB (NF-κB) inhibitor, increased the sensitivity to irinotecan of A549/CTP-11R cells. The expression level of Bcl-XL and X-linked inhibitor of apoptosis protein, target genes of NF-κB, in A549/CTP-11R cells was higher than that in A549 cells. Our result suggests that the addition of curcumin to irinotecan reverses irinotecan resistance in NSCLC.

Vascular endothelial growth factor (VEGF) plays an important role in the process of angiogenesis in many types of cancer, including non-small cell lung cancer (NSCLC), and angiogenesis inhibitors and standard chemotherapy exhibit synergy though an unknown mechanism. We therefore hypothesized that cytotoxic chemotherapy influences VEGF production and analyzed VEGF production in an NSCLC A549 cell line after treatment with standard chemotherapy. Paclitaxel inhibited the production of VEGF in A549 cells, while cisplatin and erlotinib did not. Paclitaxel and gemcitabine inhibited deferoxamine (DFX) (known to mimic hypoxia)-induced VEGF production in A549 cells. Erlotinib also inhibited DFX-induced VEGF production in A549 cells slightly, while cisplatin did not. We subsequently examined the effect of the interaction between paclitaxel or gemcitabine and VEGF protein. Paclitaxel and gemcitabine did not directly affect the binding of VEGF. Since VEGF is known as one of the HIF-1 target genes, we examined the effect of paclitaxel and gemcitabine on HIF-1α levels induced by DFX in A549 cells. Paclitaxel and gemcitabine inhibited DFX-induced HIF-1α in A549 cells. These findings may be useful for future treatment schedules, including anti-cancer agents in NSCLC.

Recent data suggested that endogenous hydrogen sulfide (H(2)S) contributes to the pathogenesis of diabetes. Here, we identified that cystathionine gamma lyase (CSE) was expressed in adipose tissue in rats and endogenously generated H(2)S. The CSE/H(2)S system exists in both rat adipocytes and pre-adipocytes. This system was up-regulated with aging, although a high level of glucose down-regulated the system in a concentration- and time-dependent manner. H(2)S inhibited the basal and insulin-stimulated glucose uptake of mature adipocytes, whereas administration of CSE inhibitors enhanced the glucose uptake of adipocytes. The PI3K but not K(ATP) channel pathway is involved in the inhibitory effect of H(2)S on glucose uptake. Finally, in fructose-induced diabetes in rats, we confirmed the up-regulated CSE/H(2)S system in adipose tissue, which was negatively correlated with glucose uptake in this tissue. Our findings suggest that H(2)S might be a novel insulin resistance regulator.

Objectives To investigate the association between air pollutants and emergency hospital visits (EHVs) for stroke in Changsha, China. Methods The daily EHVs for stroke were gathered from the third Xiangya hospital during 2008-2009. The corresponding air pollutants, meteorological data were collected. The seasonal-stratified case-crossover design with 1:1 matched pair was used to set up single-pollution models and multi-pollution models for the data analysis. Results After adjusting the temperature and relative humidity in single-pollution models, sulfur dioxide (SO 2 ) and particulate matters with an aerodynamic diameter of 10 ) were significantly association with EHVs of cerebral haemorrhage and cerebral infarction at lags of 0, 1 and 2 days in autumn. The best lag days for the effect of SO 2 on cerebral haemorrhage (OR = 1.466, 95%CI: 1.139-1.887) and cerebral infarction (OR = 1.514, 95%CI: 1.223-1.873) were lag 2 days and 0 day respectively. There were no significantly association between air pollutants and EHVs for stroke in spring, summer and winter. In multi-pollution models, an 10 μg/m 3 increase in SO 2 were significantly association with EHVs of cerebral infarction (OR = 1.587, 95%CI: 1.145-2.200) after controlling for PM 10 and NO 2 in autumn. In other seasons, there were no significantly association between air pollutants and EHVs for stroke. Conclusions Elevated the concentration of SO2, NO 2 and PM 10 in autumn were associated with EHVs for stroke in Changsha.

No curative therapy available for MMM patients apart from allogeneic hemopoietic cell transplantation(HCT). There are high morbidity and mortality in traditional allogeneic HCT. We have gotten successful RIC allogeneic HCT for a MMM patient. A man, Chinese, 37 yrs. He had anemia and on dependent transfusion and was diagnosed idiopathic MMM according to bone marrow biopsy 7 years ago. He was hospitalized on May 10, 2007. Physical exam showed pale, pencytopenia without hepatosplenomegaly. The result of X-ray on chest and electrocardiography showed anemic cardiac disease. There were some teardrop-shaped red cells on blood. His Hb was 37g/L, WBC 5.9x 109/L, Plt 33x109/L. The total volume of red cell transfusion was about 8400ml. His serum Ferritin elevated 5110 (reference

Patient is a Chinese girl of 13 years. She had fever, weakness, headache, and was hospitalized on Feb 20th, 2003. There were 0.89 leukemic monocytes in her bone marrow smear at diagnosis. She was diagnosed acute monoblastic leukemia (M5b) according to FAB classification. The immunophenotyping of bone marrow cells showed CD13 0.579, CD15 0.289, CD33 0.78, cMPO 0.27. After the second remission, she underwent hyplo-identical, ABO-matched combination transplantation of bone marrow and peripheral blood stem cells of her donor mother with T-cell deletion in Aug. 2005. Her hemapoiesis recovered at +10d after transplantation. The while complete blood cell count recovered at +31d when the TCR-PCR DNA gene map was showed the chimera. The rejection appeared at +60d. Her blood picture showed Hb 63g/L, Plt 1.0×109/L, WBC 0.4×109/L. The bone marrow picture showed hypo-cellular as same as in severe aplastic anemia. The TCR-PCR DNA gene map showed the 3/16 locus of recipient. The schedule of treatment of delayed rejection was the combination of Cyclosporin A (CsA), Mycophemolate Mofeil (MMF) and Methylprednisolone (MP). She boosted the G-CSF-primed peripheral mononuclear cells of her mother. The cell dose was 4.3×108/kg without T-deletion. Then she received the stimulation of G-CSF 250 ug daily. One week later, she suffered from Herpes Zoster Virus (HZV) infection. There was characteristic HZV varicella in full right side of head, right face, right eye, and right hand with high fever, malaise. She felt severe postherpetic neuralgia. Only morphine or remain acupuncture can relieve her severe neuralgia. She had also severe pancytopenia, gastrointestinal bleeding. We had to transfuse backed red cell and platelet concentration every week. She received first TPE at +130d and second TPE at +137d after transplantation. Dramatic results were gotten after the two TPE. After TPE she did not need transfusion again. After the third TPE, she was discharged then had treated small dose of CsA for half year. The STR-PCR DNA gene map showed the gene type from her mother. At +311d she suffered from chronic graft versus disease (cGVHD). The skin lesion involved her whole body skin about was about 50% body surface area. The effect had not received after treatment with TPE. The cGVHD had not controlled after the basic treatment with CsA or Sirolimus (FK506), MMF, MP, and Thalidomide 100–400 mg/d. So we added with ultraviolet-B irradiation (UV-B) therapy with dose of narrowbank UV-B, twice a week. The lichenification planum was disappearing. The mechanism of TPE on delayed rejection in ABO-unmatched, allogeneic stem cell transplantation has been clear. But, it is still not clear in ABO-matched and hyplo-identical allogeneic stem cell transplantation. It may be cause humoral rejection as same as ABO-incompatible stem cell or solid organ transplantation. The antibodies have resulted from hyplo-identical allogeneic stem cell of her mother. The mechanism of cGVHD results from donor T-lymphocyte activated and involves skin, liver, gut and so on. It is effective of treatment of cGVHD with immune inhibitor drugs but with TPE. Recently reported ECP is effective because the method result in suppressing the activated T-lymphocyte in recipient.

Myelofibrosis with myeloid metaplasia(MMM) is a progenitor cell colony disease. The mechanism is not very clean. The prognosis is poor in MMM patients of the traditional treatment with Hydroxyurea, Interferne, Prednisone, transfusion. Thalidomide is a new anti-angiogenesis drug of inhibiting the genesis of fibrosis. Some reports presented that the cure method only is stem cell transplantation includes autologous and allogeneic bone marrow transplantation. Patient Sui, Man, 55 years, Chinese. He was hospitalized on Aug fifth, 2004, because he has had pale, severe weakness, for 5 months. T 36.C, HR 70, R 18/min, BP114/59 mmHg. Hb56g/L, WBC 5.7x109/L, Plt 72 x109/L.There were 0.66 plasma cell in bone marrow and his bone marrow aspiration with dry draw at the diagnosis,. The result of bone marrow biopsy was fibrosis. He received 4 courses of VAD regimens (VCR 0.4mg,d1–4; ADM 10mg,d1–4, DXM 40mg d1–4) before autologous peripheral stem cell (PBSCs) transplantation. The plasma cell count decreased from 0.66 before to 0.025 after the first course of VAD regimen in the bone marrow. The stem cell mobilization regimen was chemotherapy (cyclophosphamide, Cy, 2g/m2), high-dose methylprednisolone (MP), and G-CSF 250 ug, bid d1–5. The nucleated cell count of collection showed the a minimum of 4.17x108/kg per kg of body weight, CD34+ was 0.834x106/kg.The conditional regimen was melphalan 200mg/kg divided 2 times a day and cyclophosphamide 600mg VD. He received re-transfused PBSCs on March 25,2005. His neutrophil cell decreased 0 at +4 day after transplantation. He received platelet transfusion of single donor two times when his platelet decreased 7 x 109/L. his hemotopoietic recovered at +11d. He left transplantation ward +13 d. His platelet, WBC were normal, Hb 108g/L At+d. Bone marrow draw was no dry. There was 0.07 of plasma cell in his bone marrow. The result of reticulum protein stain was degree 3 after and 4 before PBSCT at +70d. Discussion: MM is incurable tumor because the tumor cells polluted in graft of bone marrow or peripheral blood stem cells. Some author considered the pollution tumor cell decreases with high-dose MP mobilization. Mobilization of stem cell in advanced MMM is difficulty, so we (1) increased the 3 times of mobilization, (2) added high-dose of MP to mobilization regimen of combination of Cy and G-CSF. The patient had received pre-transplantation of four courses of VAD chemotherapy regimen and the combination of west and Traditional Chinese Medicine to manage during stem cell transplantation. The patient had chronic gastric ulcer so we afraid of the condition result in relapse of it so we given the patient intravenous melphalan. Some researchers studied 21 cases of multiple myeloma were treated by autologous bone marrow transplantation. The condition regimen was melphalan 16 mg/kg. The role of allogeneic BMT as compared with autologous BMT is not yet defined. The patient had been followed up for 4 months, the result showed his plasma cell was 0.07 in his bone marrow. The degree of myeloid metaplasia had changed from degree 4 to 2. Conclusion: Intensive treatment with marrow rescue could induce complete remission of long duration in some patients and provided the basis for increased attempts to cure myeloma by intentive chemoradiotherapy and BMT. It is effective in multiple myeloma treatment with autologous stem cell transplantation. The curable method is only allogeneic stem cell maybe.

100 cases of aged non-hematological anemia patients hospitalized in our hospital since July 1, 2000, were analyzed for study on anemia etiology. The mean age was 72.08+/−10.86 (60–90) years (60~ 42; 70~ 39; 80~ 18; 90~ 3) at hospitalization. The etiology of anemia with known showed as followed: Malignant tumor 34: included digestive system malignant tumor 27 (gastric cancer 7, rectal carcinoma 7, colon cancer 6, liver cancer 3, cholangiocarcinoma 2, pencreatic duct cancer 2), lung cancer 3, urinary tract cancer 2, bone sarcoma 2. Iron deficiency anemia 47: digestive tract ulcer 16, hemorrhoid 14. The total number of iron deficiency anemia includes digestive tumors with bleeding. Single nutrition deficiency anemia, macrocytic anemia, i.e. vitamin B12 and/or folic acid deficiency (non-malignant, Non-iron deficiency anemia) 8. Inherited Anemia 10: Thalassemia 6, Glucose-6-phosphate dehydrogenase (G6PD) deficiency 4. Chronic diseases 23: Bone fracture 19, Stroke 18, infection 12, Diabetes 10, Kidney function failure 8, Gynecological bleeding 4. The etiology of anemia is unknown 29: it included some chronic diseases with anemia. Discussion: Incidence of malignant tumor is very high. The incidence of malignancy was 34% in the series of aged anemia. The chance of gene mutation increased as patients’ age getting older. When to diagnose aged anemia, we should better to consider that the primary disease is tumor maybe, and look for tumor carefully. Mechanism of anemia in patients with tumor Gastrointestinal tumor with chronic bleeding that can result in anemia. But, there is serious anemia without bleeding in our series. There were some different chronic diseases in 34 cases of tumor. Researchers have discovered that structural and metabolic disorders were detected in mature erythrocytes in patients with and without anemia in stomach cancer. Anemia development pathways were dependent on enhanced hemolysis of circulating erythrocytes and influx of immature cells from the bone marrow. Complication of etiology in aged anemia Etiological diseases of aged anemia is different and complicate. The major of aged anemia has two or more primary diseases. The primary presenting of gastrointestinal tumor maybe is iron deficiency anemia. The tumor with anemia can result from nutritional deficiency at advance. For example, there were vitamin B12 or/and folic acid 8 cases in our aged series. Some anemia patients in our series complicated cardiac disease, stroke, and bone fracture. 2 cases of G6PD deficiency had primarily diagnosed when they suffered from infection at very old age, 70 years or more in these aged anemia. There are 100 million G6PD in whole world, the incidence is very high especially in Africa and South China. Diagnosis should make as soon as possible. Many advanced tumors were incurable. About 20 per cent of patients with carcinoma of the colon or rectum present with metastatic disease. Surgeons are frequently asked to consider resection or other operative procedures in these patients for palliation. But, average survival was 11.2 months for operative patients versus 6.5 months for nonoperative patients (P < 0.05). So we should better discover tumor anemia and differentiate from other benign anemia in the aged anemia as soon as possible for curable section. To pay attention to treat of etiological diseases is very important for aged anemia patients.