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Drug-induced liver injury (DILI) is a leading cause of therapy failure in the clinic and also contributes much to acute liver failure cases. Investigations of predictive sensitivity in animal models have limitations due to interspecies differences. Previously reported in vitro models of liver injury based on primary human hepatocytes (PHHs) cannot meet the requirements of high physiological fidelity, low cost, simple operation, and high throughput with improved sensitivity. Herein, we developed an integrated biomimetic array chip (iBAC) for establishing extracellular matrix (ECM)-based models. A collagen-based 3D PHH model was constructed on the iBAC as a case for the prediction of clinical DILI at throughput. The iBAC has a three-layer structure with a core component of 3D implanting holes. At an initial cell seeding numbers of 5000-10,000, the collagen-based 3D PHH model was optimized with improved and stabilized liver functionality, including cell viability, albumin, and urea production. Moreover, basal activities of most metabolic enzymes on the iBAC were maintained for at least 12 days. Next, a small-scale hepatotoxicity screening indicated that the 3D PHH model on the iBAC was more sensitive for predicting hepatotoxicity than the 2D PHH model on the plate. Finally, a large-scale screening of liver toxicity using 122 clinical drugs further demonstrated that the collagen-based 3D PHH model on the iBAC had superior predictive sensitivity compared to all previously reported in vitro models. These results indicated the importance of 3D collagen for liver physiological functionality and hepatotoxicity prediction. We anticipant it being a promising tool for risk assessment of drug-induced hepatotoxicity with a widespread acceptance in drug industry.

Peptide drug conjugate (PDC) has emerged as one of the new generations of targeted therapeutics for cancer, which owns the advantages of improved drug targetability and reduced adverse effects compared with traditional chemotherapy. However, the poor permeability of PDC drugs regarding tumor cells is an urgent problem to be solved. Herein, we design a PDC drug molecule, which is composed of three modules: targeting motif (RGD target), assembly motif (GNNNQNY) and cytotoxic payload (CPT molecule). This PDC in situ forms nanoclusters upon binding cellular receptor, resulting in improved PDC cell-entry efficiency and treatment efficacy. In addition, the PDC shows increased therapeutic efficacy and raises the maximum tolerance dose of the drug in breast and bladder xenografted mice models. This strategy leverages the assembly principle to promote penetration of peptide molecules into cells and increase intracellular drug bioavailability, which is of great significance for the development of PDC drugs in the future.

The indicators for measuring vitamin D are various, and 25-hydroxyvitamin D (25(OH)D) is considered as the optimal indicator of total vitamin D levels. In this study, we aim to deeply explore the 25(OH)D status in systemic lupus erythematosus (SLE) patients, and evaluate its relation to SLE risk and disease severity.Literature about 25(OH)D status and its associations with SLE were searched in Pubmed, Embase and Cochrane Library databases. Standardized mean difference (SMD), odds ratio (OR) and corresponding 95% confidence interval (95% CI) were illustrated by forest plots, and correlation coefficients (r) were combined by generic inverse variance method. Heterogeneity and publication bias were quantified by I-squared (INineteen articles were included into our meta-analysis. The overall results showed that compared with the healthy controls, the circulating 25(OH)D levels were significantly lower in SLE patients (pooled SMD = -1.63, 95% CI: -2.51 to -0.76). Subgroup analysis revealed that compared with the healthy controls, SLE patients of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥ 10, Arab and European ethnicity, all 4 seasons, no vitamin D supplement, had significantly lower circulating 25(OH)D levels; no significant differences were observed in SLE patients of SLEDAI 10, mixed ethnicity, spring, summer, vitamin D supplement, respectively; no matter the changes of age, disease duration, and the therapy of corticosteroid or immunosuppressive or neither, circulating 25(OH)D levels were significantly reduced in SLE patients. The deficiency, insufficiency and sufficiency of vitamin D could significantly elevate, slightly decrease (not significantly), significantly decrease SLE risk, respectively (pooled OR = 4.37, 95% CI: 1.49 to 12.84; pooled OR = 0.52, 95% CI: 0.22 to 1.26; pooled OR = 0.31, 95% CI: 0.15 to 0.63). Circulating 25(OH)D levels were inversely associated with SLEDAI (pooled correlation coefficient = -0.50, 95% CI: -0.8278 to -0.1689).Compared with healthy controls, 25(OH)D levels are significantly lower in SLE patients, which is influenced by disease activity, ethnicity, seasons and vitamin D supplement; no matter the change of age, diseases duration and therapy of corticosteroid or immunosuppressive or neither, 25(OH)D levels are significantly decreased in SLE patients; the deficiency, insufficiency and sufficiency of vitamin D could significantly elevate, slightly decrease, and significantly decrease SLE risk, respectively; and 25(OH)D levels inversely correlate with SLEDAI.

Summary: Objective: To explore the quantitative measurements and evaluation of intra-peritoneal fat distribution by MDCT and its significance in predicting intra-operative bleeding volume during D2 lymphadenectomy in gastric cancer (GC) patients. Methods: From June 2016 to September 2017, GC patients scheduled for open gastrectomy with D2 lymph-node dissection were enrolled. According to the BMI, the subjects were then classified as normal BMI(BMI

Given the therapeutic efficacy of fasudil hydrochloride (F) and dichloroacetate (DCA) on pulmonary arterial hypertension (PAH), a new salt fasudil dichloroacetate (FDCA) was designed, synthesized and biologically evaluated. FDCA exhibited comparable ROCK II inhibitory activity relative to fasudil hydrochloride, and suppressed the expression of TNF-α and IL-6 in both PDGF-BB and hypoxia-treated pulmonary arterial smooth muscle cells (PASMCs) and endothelial cells (PAECs). Significantly, FDCA lowered mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), and decreased right ventricular hypertrophy (RVH) in monocrotaline (MCT)-induced PAH rats. Meanwhile, FDCA remarkably decreased pulmonary artery medial thickness (PAMT) and hyperplasia, restoring the elasticity of elastic fiber, reduced cardiac hypertrophy, and attenuated fibrosis of heart and lung. Collectively, FDCA exhibited triple activities of pulmonary vasodilation, vascular remodeling inhibition and RVH inhibition, suggesting that it may be a promising agent for PAH intervention.

Objectives: The aim of this study is to investigate the prognostic significance of baseline maximum standard uptake value (SUVmax), whole body SUVmax (WBSUVmax), whole body metabolic tumor volume (WBMTV) and whole body total lesion glycolysis (WBTLG) in patients with peripheral T-cell lymphoma (PTCL). Methods: Eighty patients with PTCL who underwent pretreatment 18F-PET/CT were enrolled in this study. WBMTV and WBTLG were computed by using the margin threshold of SUV>3.0. WBSUVmax was obtained by summing of SUVmax of the whole-body SUVmax of 11 nodal and 10 extra-nodal lesions. Results: Median SUVmax was 13.8 (range, 4.6-35.5), median WBSUVmax was 24.6 (range, 4.6-153.4), median WBMTV was 149 cm3 (range, 4-4545 cm3) and median WBTLG was 1017 (range, 16.5-23739). Six patients with anaplastic large cell lymphoma, ALK positive were excluded in the following statistical analysis for their unique pathological types and good prognosis. The receiver operating curve (ROC) analysis showed that the optimal cut-off values of WBSUVmax, WBMTV and WBTLG with overall survival (OS) were 22.2, 169.5 cm3 and 746.1, respectively. Patients with high WBSUVmax, WBMTV and WBTLG had a poor prognosis. WBSUVmax, WBMTV and WBTLG were associated with international prognostic index (IPI) and prognostic index for T-cell lymphoma (PIT). In multivariate analysis, WBTLG and PIT were independent prognostic factors of both progression free survival (PFS) and OS. Conclusions: Our study shows that high WBTLG, WBMTV and WBSUVmax could predict a relatively poor prognosis, and has a highly significant association with PIT and IPI.WBTLG could be an independent predictive factor for survival outcomes in patients with PTCL.

Background There were few reports on the lymph nodes of entrance point to recurrent laryngeal nerve (LN-epRLN) in patients with papillary thyroid carcinoma (PTC). Therefore, we aimed to increase awareness of LN-epRLN. Methods A prospective analysis including 878 consecutive patients with PTC who underwent thyroidectomy from April 2016 to March 2017 was performed. We explored the surrounding tissue of entrance point to recurrent laryngeal nerve, during routine central lymph node dissection (CLND). The lymph node specimens were sent separately for routine histopathological examination, and the complications and follow-ups were recorded. Results LN-epRLN was found in 73 of the 878 patients and the metastasis rate was 3.76%. In univariate analysis, LN-epRLN metastasis was correlated with further central nodal metastasis, tumor location in the upper third of the thyroid and tumor multifocality. Conclusions LN-epRLN can be the site of metastasis of PTC. CLND scope should include the surrounding tissue of entrance point to recurrent laryngeal nerve. LN-epRLN metastasis in PTC is associated with tumor location in the isthmus or upper third of the thyroid, tumor multifocality and further central nodal metastasis.

Background and Aims: Matrix metalloproteinase-9 (MMP-9) is closely related to the pathogenesis of autoimmune diseases, especially Systemic Lupus Erythematosus (SLE). However, published works about the circulating MMP-9 levels in SLE are contradictory. A meta-analysis was performed to estimate circulating MMP- 9 levels in SLE patients more accurately and explore its related influencing factors. Methods: The related literatures were systematically searched in PubMed, Embase, and The Cochrane Library database (up to 31 January 2018). Pooled Standardized Mean Difference (SMD) and 95% Confidence Interval (CI) of circulating MMP-9 levels were calculated by Stata12.0 software according to fixed-effect or randomeffect model analysis. Results: A total of 638 articles were retrieved, and 12 studies including 730 SLE cases and 759 controls were finally included in the meta-analysis. No significant differences in circulating MMP-9 levels were observed between SLE patients and healthy controls (pooled SMD = -0.209, 95% CI = -0.812 to 0.394). However, subgroup analyses indicated that age Conclusion: The meta-analysis of current evidence suggests that circulating MMP-9 levels do not differ between SLE patients and healthy controls, however, the results may be affected by age and sample size. Further studies are needed to clarify the relationship between SLE and circulating MMP-9 levels.

Whether Chinese herbal formulas are effective in treatment of postmenopausal osteoporosis remains unclear. The aim of this study is to explore the experimental evidence of both in vitro and in vivo preclinical studies using Chinese herbal formulas in postmenopausal osteoporosis. Searches were applied to various databases with relevant keywords. Original in vivo and in vitro studies using Chinese herbal formulas to treat postmenopausal osteoporosis, and with full text available, were included. Er-Xian Decoction, Bu-Shen-Ning-Xin Decoction, Qing E Formula, Liuwei Dihuang Wan, and Xian-Ling-Gu-Bao Decoction, the most commonly studied formulas, were selected from the pool of Chinese medicine. The preclinical data indicated the potential use of Chinese herbal formulas in postmenopausal osteoporosis. The underlying mechanisms included bone morphogenetic protein (BMP), Wnt/[Formula: see text]-catenin, extracellular-signal-regulated kinase/c-Jun [Formula: see text] terminal kinase/mitogen-activated protein kinase (ERK/JNK/MAPK), estrogen receptor (ER), and osteoprotegerin/receptor activator of nuclear factor [Formula: see text]B ligand (OPG/RANKL) signaling pathways. This study demonstrated the anti-osteoporotic effect of Chinese herbal formulas targeting different pathways in bone metabolism. Further study with adequate sample size and follow-up time, appropriate controls, and optimal blinding is required.

Purpose of the study Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility. Study design We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA. Results The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes. Conclusions The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA.

Currently, there is no effective therapy for the treatment of highly metastatic triple-negative breast cancer (TNBC). Microvesicle (MV) formation is crucial for the metastasis of TNBC. Here we report a novel strategy to inhibit the generation of MVs for the intervention of TNBC. O2-3-Aminopropyl diazeniumdiolates 3a–f are designed and synthesized, which can be activated by lysyloxidase over-expressed in TNBC cells. The most active compound 3f is able to selectively release high levels of NO in TNBC cells, inhibit the cell proliferation, and reduce the adhesion, invasion and migration of TNBC cells in vitro. Furthermore, 3f significantly suppresses the growth and metastasis of implanted TNBC in vivo through attenuating MV formation by an epigenetic modification of miR-203/RAB22A expression in an NO-dependent manner, providing the first evidence of NO donor(s) acting as epigenetic modulators to fight highly metastatic TNBC.

Clinical toxoplasmosis in AIDS/HIV patients is a great public health concern around the world. Untreated Toxoplasma gondii (T. gondii)-infections are often fatal in AIDS/HIV patients. This study aims to assess the seroprevalence and odds ratio (OR) of T. gondii in AIDS/HIV patients, as well as the potential influential factors. Studies published from December 1, 1983 to December 1, 2016 in English, which comparing the seroprevalence of T. gondii between AIDS/HIV patients and control group were searched in PubMed, EMBASE and The Cochrane Library databases. The non-weighted prevalence, pooled fixed-effect or random-effect model estimates of OR and its 95% confidence intervals (CI) were all calculated. Heterogeneity test was performed by the Q statistic and quantified using I2, publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 4220 articles were obtained after searching databases, and 12 studies with 2101 AIDS/HIV patients and 5851 controls were incorporated in the meta-analysis. Meta-analysis revealed that, compared with the control group, the AIDS/HIV group had a higher seroprevalence of T. gondii (46.12% vs 36.56%) (OR=1.55, 95%CI: 1.19-2.04). Subgroup analyses showed that publication year, race, geographic locations and diagnostic methods are positive associated with the seroprevalence of T. gondii. Overall, our study suggests that AIDS/HIV patients have higher seroprevalence of T. gondii than those without.

Increasing evidence has demonstrated the association between long noncoding RNAs (lncRNAs) and multiple autoimmune diseases. To explore four lncRNAs (GAS5, lnc-DC, linc0597 and linc0949) expression levels and gene polymorphisms in systemic lupus erythematosus (SLE), a two stage design was applied. In the first stage, 85 SLE patients and 71 healthy controls were enrolled to investigate the lncRNAs expression levels. Then, 1260 SLE patients and 1231 healthy controls were included to detect the single nucleotide polymorphisms (SNPs) in the differentially expressed lncRNAs identified in the first stage. Linc0597, lnc-DC and GAS5 expression levels were significantly lower in SLE patients than healthy controls (P P P = 0.003 respectively). Association of five SNPs (rs10515177, rs2070107, rs2632516, rs2877877, rs2067079) with SLE risk were analyzed. No significant association was observed between these gene polymorphisms and susceptibility to SLE (all P > 0.010), and we did not find significant association between any genotypes at five SNPs and their respective lncRNAs expression in SLE (all P > 0.010). In summary, the expression levels of linc0597, lnc-DC and GAS5 are decreased in SLE patients, but their gene polymorphisms are not associated with SLE risk, and do not influence their expression levels.

This study aimed to systemically review the evidence regarding the relationship between the circulating blood osteoprotegerin (OPG) level and rheumatoid arthritis (RA), as well as the potential influential factors. Research related to plasma/serum OPG levels in RA patients and healthy controls were gathered using PubMed, EMBASE, and The Cochrane Library database (up to Jan. 1, 2017). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2, and publication bias was evaluated using a funnel plot and Egger's linear regression test. After searching databases, 443 articles were obtained, and 11 studies with 710 RA patients and 561 controls were finally included. Meta-analysis revealed that, compared with the control group, the OPG level was significantly higher in the RA group (P

Aim Studies investigating the association between HLA-DQB1 alleles and rheumatoid arthritis (RA) have reported conflicting results. The purpose of this study was to evaluate whether DQB1 alleles confer susceptibility to RA. Design A comprehensive literature search up to May 2016 was conducted to identify case-control studies on the association of HLA-DQB1 alleles with RA. Pooled ORs with 95% CIs were used to assess the strength of association. Setting The literature indicates that HLA-DQB1 is associated with susceptibility to RA. Main outcome measures Frequencies of HLA-DQB1 alleles and phenotype in RA patients and healthy controls. Results Fifteen studies with 1250 cases and 1621 controls were included in this meta-analysis. DQB1 alleles were associated with RA susceptibility. The frequencies of DQB1*06 were lower in RA (p-value for comparability=0.007, OR 0.726,95% CI 0.576 to 0.916; p=0.004, OR 0.611,95% CI 0.438 to 0.852). The frequencies of DQB1*02 were lower in RA (p=0.044, OR 0.731,95% CI 0.597 to 0.895). A higher frequency of DQB1*04 was observed in RA (p=0.023, OR 1.604,95% CI 1.067 to 2.410). Conclusions This meta-analysis demonstrates that DQB1*02 and DQB1*06 may be negatively associated with RA. Conversely, DQB1*04 may confer susceptibility to RA.

HuoXueJieDu (HXJD) formula exerts protective effects against diabetic retinopathy (DR) in rats, but its underlying mechanism remains unknown. In the present study, the diabetic rats were established using streptozocin. The administration of HXJD was initiated at 20 weeks after diabetes induction and continued for 12 weeks. Whole genome expression profiles in rat retinas were examined using microarray technology. Differential gene expression and pathway enrichment analysis were conducted on the microarray data, with validation through real-time PCR and immunohistochemical staining. The results showed that 170 genes and several IPA canonical pathways related to inflammation, matrix metabolism, and phototransduction were regulated by HXJD. PCR validation of selected genes, including SOCS3, STAT3, TIMP1, and A2M, confirmed the gene expression changes influenced by HXJD. In addition, the immunohistochemical staining results suggested that critical members of the SOCS3-STAT3 pathway were also affected by HXJD. Taken together, these results indicated that SOCS3-STAT3 and TIMP1-A2M pathways might mediate the alleviation of HXJD activities in rats with diabetic retinopathy.

The new nitric oxide (NO) donor O2-(6-oxocyclohex-1-en-1-yl)methyl diazen-1-ium-1,2-diolate 3c could simultaneously liberate NO as well as an active 3-glutathionyl-2-exomethylene-cyclohexanone 2 in the presence of GSH/GSTπ; exhibit potent antiproliferative activity; repress migration, invasion, and lateral migration of metastatic B16–BL6 cells; and significantly decrease hetero-adhesion of B16–BL6 cells to human umbilical vein endothelial cells.

// Jin-Hua Liang 1, * , Chong-Yang Ding 2, * , Robert Peter Gale 3 , Li Wang 1 , Ji Xu 1 , Xiao-Yan Qu 1 , Lei Fan 1 , Tian-Lv Li 2 , Jian-Yong Li 1, 4 , Wei Xu 1 1 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China 2 Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China 3 Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom 4 Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Jian-Yong Li, email: lijianyonglm@medmail.com.cn Wei Xu, email: xuwei10000@hotmail.com Keywords: PET/CT, extranodal NK/T-cell lymphoma, prognosis, SUVmax Received: June 13, 2016 Accepted: November 12, 2016 Published: December 10, 2016 ABSTRACT We analyzed data from 54 newly-diagnosed persons with extra-nodal natural killer/T-cell (NK/T) lymphoma, who had a pretreatment 18 F-FDG PET/CT study, to determine whether the sum of SUVmax of all the nodal and extra-nodal lesions predicted progression-free survival (PFS) and/or overall survival (OS). Three models (WB1SUVmax, WB2SUVmax, WB3SUVmax) based on the basis of the sum of SUVmax of the whole-body SUVmax of 11 nodal and 10 extra-nodal lesions were tested. The discrimination value of these models was evaluated using time-dependent receiver-operator characteristic (ROC) curves and corresponding areas under the curve (AUC) in training and validation cohorts. Findings were validated in an independent cohort of 15 subjects. ROC curve analysis showed the optimal cut-off values for WB1SUVmax, WB2SUVmax and WB3SUVmax were 15.8 (sensitivity 92%, specificity 67%, AUC 0.811; P

Sleep staging is an important basis for the diagnosis of sleep disorders and other related diseases. An auto sleep staging method based on multi-parameter features fusion was proposed. First, using the Discrete Wavelet Transform (DWT) to filter the raw signals, obtain 8 features of sleep staging. Then the parameters of features were inputted to Support Vector Machine (SVM) for training and classification. Finally, using the cross-validation to model different samples for verifying the generalization ability. The results show that the accuracy of the method reach 93.08%, which is 9.39% higher than based EEG, and reached 85.25% with cross-validation, that indicated a better generalization ability.

Cardiovascular (CV) risk in type 1 diabetes mellitus (T1DM) is increased. In this study, we evaluated the differences in major markers of CV risk between patients with T1DM and healthy controls by a systematic review and meta-analysis. Literature from PubMed, EMBASE, and The Cochrane Library comparing CV risk markers between patients with T1DM and controls was obtained. The overall standard mean differences (SMDs) of carotid intima–media thickness (cIMT), endothelium-dependent flow-mediated dilation (FMD%), carotid-femoral pulse wave velocity (cf-PWV), and glyceryl trinitrate-mediated dilatation (GTN%) with its 95% confidence interval (CI) between patients with T1DM and control groups were calculated using fixed-effect or random-effect model. Heterogeneity was evaluated using the Cochran Q and I2 statistics. The results showed that patients with T1DM had a significantly greater cIMT (SMD: 0.89; 95% CI, 0.69-1.09; P < .001), significantly lower FMD% (SMD: −1.45%; 95% CI, −1.74 to −1.17; P < .001), significantly increased cf-PWV (SMD: 0.57; 95% CI, 0.03-1.11; P < .001), and significantly decreased GTN% (SMD: −1.11; 95% CI, −1.55 to −0.66; P < .001) than controls. Our results support the current evidence for an elevated CV burden in patients with T1DM and affirm the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

Breast cancer stem cells (BCSCs) are believed to be responsible for tumor chemoresistance, recurrence, and metastasis formation. Salinomycin (SAL), a carboxylic polyether ionophore, has been reported to act as a selective breast CSC inhibitor. However, the molecular mechanisms underlying SAL-induced cytotoxicity on BCSCs remain unclear. The Hedgehog (Hh) signaling pathway plays an important role in CSC maintenance and carcinogenesis. Here, we investigated whether SAL induces cytotoxicity on BCSCs through targeting Hh pathway. In the present study, we cultured breast cancer MCF-7 cells in suspension in serum-free medium to obtain breast CSC-enriched MCF-7 mammospheres (MCF-7 MS). MCF-7 MS cells possessed typical BCSC properties, such as CD44+CD24-/low phenotype, high expression of OCT4 (a stem cell marker), increased colony-forming ability, strong migration and invasion capabilities, differentiation potential, and strong tumorigenicity in xenografted mice. SAL exhibited selective cytotoxicity to MCF-7 MS cells relative to MCF-7 cells. The Hh pathway was highly activated in BCSC-enriched MCF-7 MS cells and SAL inhibited Hh signaling activation by downregulating the expression of critical components of the Hh pathway such as PTCH, SMO, Gli1, and Gli2, and subsequently repressing the expression of their essential downstream targets including C-myc, Bcl-2, and Snail (but not cyclin D1). Conversely, Shh-induced Hh signaling activation could largely reverse SAL-mediated inhibitory effects. These findings suggest that SAL-induced selective cytotoxicity against MCF-7 MS cells is associated with the inhibition of Hh signaling activation and the expression of downstream targets and the Hh pathway is an important player and a possible drug target in the pathogenesis of BCSCs.

Accumulating evidence has linked long noncoding RNAs (lncRNAs) to autoimmune and inflammatory disorders. This study aimed to detect the expression levels of five lncRNAs (lnc0640, lnc3643, lnc5150, lnc7514 and lncagf) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as their correlation with clinical and laboratory features.We recruited 76 patients with SLE and 71 normal controls into the present study, and obtained PBMCs from the blood samples of all study subjects. Expression levels of lncRNAs were determined by quantitative real-time reverse transcription polymerase chain reaction and their associations with clinical and laboratory characteristics were analyzed.Lnc5150 expression levels were statistically significantly decreased (Z=-6.016, P 0.001) compared with normal controls. Lnc3643 levels were also statistically significantly decreased in SLE patients with proteinuria compared with those without (Z=-2.934, P = 0.003), and the lnc7514 levels were statistically significantly lower in anti-dsDNA(+) patients compared with anti-dsDNA(-) patients. The expression levels of lnc3643 were correlated with C-reactive protein and erythrocyte sedimentation rate (ESR), lnc7514 was correlated with disease activity and ESR (all P 0.01).The aberrant lncRNA expression levels and their associations with laboratory features in SLE suggest their important role in SLE pathogenesis.

The aim of this study was to investigate the association of interleukin (IL)-10 gene single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. 848 SLE patients and 461 normal controls were recruited in this study. Nine SNPs in IL-10 gene (rs1518110, rs1518111, rs1554286, rs1800890, rs1800893, rs3024493, rs3024495, rs3024498 and rs6667202) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The frequency of IL-10 rs3024498-C allele was significantly higher in patient group compared with control subjects (OR=5.118, 95% CI=1.819-14.405, P=0.002). No significant differences were detected for the distribution of allele and genotype frequencies of other eight SNPs between patients with SLE and controls after Bonferroni correction (all P>0.0056). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs3024498 between SLE patients with and without arthritis (P=0.002, P=0.022, respectively).There was significant difference in genotype frequency at rs3024498 between SLE patients with and without malar rash (P=0.040). And, there was significant difference in allele frequency at rs3024498 between SLE patients with and without anti-double-stranded DNA (P=0.032). Meanwhile, significant difference in genotype frequency at rs1518110 and rs1518111 were found in patients with and without lupus headache (P=0.025, P=0.038, respectively). There were significant difference in allele and genotype frequency at rs1800890 and rs6667202 between SLE patients with and without thrombocytopenia (rs1800890: P=0.016, P=0.026, respectively; rs6667202: P=0.007, P=0.007, respectively). Further, significant difference were observed both in allele frequency and in genotype distribution of rs1800893 between patients with and without tubular urine and proteinuria (tubular urine: P

SummaryObjective Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma with a favorable clinical outcome. For unilateral PTC patients with thyroid nodules in the contralateral lobes, the necessity of total thyroidectomy (TT) is still in doubt. In this study, we aimed to define clinical factors that could be indicators for malignancy in nodules in the contralateral thyroid lobe, which could aid the clinician in selecting the appropriate operation approach. Design, Patients and Measurements This is a retrospective study from Jan 2014 to Dec 2016 conducted in Shanghai Ruijin Hospital. 1442 cases with unilateral PTC and ultrasonographically benign nodules in the contralateral lobe who underwent TT at a single institution were enrolled. All patients underwent preoperative ultrasonography (US) and all the cases were confirmed by board-certified pathologists. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality, central lymph node metastases and BRAF mutation were examined to evaluate the rate of malignancy in the contralateral thyroid nodules. Results In total, 47% of patients (677 cases)were confirmed to have malignancy in the contralateral lobe. Univariant analysis indicated that capsular invasion, Hashimoto's thyroiditis, multifocal loci, central lymph node metastases as well as BRAF mutation predicted a high incidence of occult contralateral carcinoma. Multivariant analysis showed capsular invasion, multifocal ipsilateral thyroid lobe, central lymph node metastases as well as BRAF mutation can serve as independent predictors for malignancy in the contralateral thyroid lobe. Conclusions Malignancy in the contralateral lobe was found in 47% of patients. This finding was associated with multifocal primary carcinomas involvement, capsular invasion, Hashimoto's thyroiditis history, central lymph node metastases and BRAF mutation, which should therefore be taken into consideration when planning therapeutic strategy for the patients. This article is protected by copyright. All rights reserved.

Background The Hippo signaling pathway is reported to be involved in angiogenesis, but the roles of the Hippo pathway in diabetic retinopathy have not been addressed. Fufang Xueshuantong Capsule has been used to treat diabetic retinopathy in China; however, the effect of Fufang Xueshuantong Capsule on the Hippo pathway has not been investigated. Methods In this study, diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Twenty weeks later, Fufang Xueshuantong Capsule was administered for 12 weeks. When the administration ended, the eyes were isolated for western blot and immunohistochemistry analyses. The levels of P- mammalian sterile 20-like (MST), large tumor suppressor homolog (Lats), P- yes-associated protein (YAP), transcriptional co-activator with PDZ binding motif (TAZ) and TEA domain family members (TEAD) were measured. Results Diabetic rats had a decreased P-MST level in the inner plexiform layer and reduced expression of P-YAP in the photoreceptor layers of their eyes. In addition, diabetic rats displayed remarkable increases in Lats, TAZ and TEAD in their retinas. Furthermore, Fufang Xueshuantong Capsule restored the changes in the Hippo pathway. Conclusions The Hippo signaling pathway is important for the progression of diabetic retinopathy and will hopefully be a targeted therapeutic approach for the prevention of diabetic retinopathy. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1678-3) contains supplementary material, which is available to authorized users.

OBJECTIVE To determine whether X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted to determine the associations between XRCC1 gene polymorphisms and susceptibility to SLE and RA. METHODS A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. RESULTS A total of nine case-control articles, consisting of five SLE and four RA articles, involving 1138 patients and 1399 healthy controls, were included in the meta-analysis. This meta-analysis showed no significant association of the Arg399Gln and Arg194Trp polymorphisms with SLE were found in all models when all study subjects were considered together. Stratification by ethnicity indicated the variant Arg399 (A) allele carriers increased the risk of SLE in Asians (A vs. G: OR = 1.402, 95% CI = 1.139-1.726, P = 0.001) and decreased the risk of SLE in Caucasians (A vs. G: OR = 0.769, 95% CI = 0.630-0.937, P = 0.009; AA vs. AG+GG: OR = 0.727, 95% CI = 0.554-0.953, P = 0.021). However, we failed to reveal any association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk under all analysis models. Similar results were obtained in the subgroup analysis based on ethnicity. CONCLUSIONS The present study suggests that the XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE in Asians and Caucasians, and there is no significant association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk.

Energetic particle precipitation (EPP) has significant impacts on ozone depletion in the polar middle atmosphere during geomagnetic activity. It is well known that solar ultraviolet (UV) radiation plays an important role in ozone generation. Therefore, it is interesting to compare the contributions of EPP and solar UV to ozone changes in the polar upper atmosphere. In this article, we use the annual average Ap index to denote the annual-mean magnitude of the geomagnetic activity, which is closely correlated with the EPP flux, and the annual average F10.7 index to denote the annual-mean magnitude of the solar radiation, which is somewhat related to the solar UV. We adopt the 5° zonal annual-mean ozone profile dataset to study the statistical characters between the ozone dataset and the Ap, F10.7 indices. Multiple regression analysis shows that the contributions of geomagnetic activity are not negligible and are of a similar order of magnitude as the solar UV radiation in the polar upper atmosphere (above 10 hPa). The results also show that high-speed solar-wind-stream-induced and coronal-mass-ejection-driven geomagnetic activity is of the same order of magnitude. There are interhemispheric differences according to our multiple regression analysis. We discuss the possible causes of these differences.

The aim of this research is to investigate the therapeutic effect of GGQL decoction on cardiac dysfunction and elucidate the pharmacological mechanisms. db/db mice were divided into DB group or GGQL group, and WT mice were used as control. All mice were accessed by echocardiography. And the total RNA of LV tissue samples was sequenced, then differential expression genes were analyzed. The RNA-seq results were validated by the results of RT-qPCR of 4 genes identified as differentially expressed. The content of pyruvate and ceramide in myocardial tissue was also measured. The results showed that GGQL decoction could significantly improve the diastolic dysfunction, increase the content of pyruvate, and had the trend to reduce the ceramide content. The results of RNA-seq showed that 2958 genes were differentially expressed when comparing the DB group with the WT group. Among them, compared with the DB group, 26 genes were differentially regulated in the GGQL group. The expression results of 4 genes were consistent with the RNA-seq results. Our study reveals that GGQL decoction has a therapeutic effect on diastolic dysfunction of the left ventricular and the effect may be related to its role in promoting myocardial glycolysis and decreasing the content of ceramide.

Based on high selectivity of mass spectrum, a method of chromatogram baseline-shift elimination was proposed and applied to study the interference of the baseline-shift on the metabonomics of liver toxicity caused by acetaminophen (APAP) and carbon tetrachloride (CCl4), and the metabonomics model-based evaluation of drug toxicity. The chromatogram baseline obtained by this method was true in all ranges of the retention time, including the ranges of chromatographic peaks. Besides, it could express the baseline-shift with the heteroscedastic noise, which was usually contained in the chromatographic peak and grew with the signal intensity of the peak. The metabonomics models of liver toxicity were built according to total ion chromatograms of urine samples from APAP, CCl4 and normal groups, whose baseline-shift was eliminated by this method. The result showed that baseline-shift would lead to a reduction of the evaluated toxicity and then may result in a wrong evaluation of drug toxicity.

Pulmonary hypertension (PH) has been suggested to be associated with systemic lupus erythematosus (SLE). However, the results of prevalence studies on PH in SLE vary substantially. To derive a more precise estimation on the prevalence of PH in SLE, a meta-analysis was performed. Relevant literatures were searched in PubMed and EMBASE until November 2017. A total of 1366 articles were obtained after searching databases, and 23 studies were finally included in the meta-analysis. Heterogeneity test was performed, and publication bias was evaluated. The result of analysis in random effect model showed that the pooled prevalence was 8% (95%CI 5–12%). There was no evidence of publication bias (p = 0.51). To evaluate the stability of our results, sensitivity analyses were performed, and the results showed no significant change when any one study was excluded. Subgroup analyses demonstrated that there were significant differences in PH prevalence in SLE patients of different gender, age, regions, year of publication, and diagnostic methods. PH is prevalent in SLE patients, but it was significantly different between different gender, age, regions, year of publication, and diagnostic methods.

Ethnopharmacological relevance Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis are popular plants used in traditional Chinese medicine to treat diabetes. Aim of the study The aim of the study is to investigate the therapeutic effect of the active components of Euonymus alatus, Radix trichosanthis, Panax notoginseng and Coptis chinensis (cERPC) on diabetic peripheral neuropathy in the rats and explore the underlying mechanism involved. Methods After diabetes was induced in rats for 20 weeks, cERPC or water was administered for 12 weeks. After a hot plate test, motor nerve conduction velocity and sciatic nerve blood flow were determined; the sciatic nerves were isolated for toluidine blue staining; and the fibre area, fibre diameter, axon area, axon diameter and myelin thickness were evaluated. The levels of the myelin basic protein, myelin protein zero, Oct6 and Krox20 were measured by western blot or immunofluorescence. Results cERPC was efficient in reducing the response latency, increasing motor nerve conduction velocity, enhancing sciatic nerve blood flow and ameliorating the pathological changes in diabetic rats. cERPC also had a role in increasing the levels of myelin basic protein and myelin protein zero and improving the expression of Oct6 and Krox20 in sciatic nerves of diabetic rats. Conclusions cERPC ameliorates diabetic peripheral neuropathy by attenuating electrophysiological, circulatory and morphological alterations, which is mediated by the Oct6-Krox20 pathway.

Prolactin (PRL), a polypeptide hormone produced by the pituitary gland, is involved in the regulation of humoral and cell mediated immune responses. PRL levels have been investigated in several autoimmune diseases including systemic lupus erythematosus (SLE), however, yielded different and inconsistent results. This study aims to derive a more precise evaluation on plasma/serum PRL levels in SLE patients, as well as the potential influential factors.Studies published from 1 January 1987 to 31 December 2015 in English, which comparing plasma/serum PRL levels between SLE group and control group were searched in PubMed, EMBASE and The Cochrane Library databases. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using IFive-hundred and forty-seven articles were obtained after searching databases, and 12 studies with 429 SLE patients and 326 controls were finally included. Meta-analysis revealed that, compared with the control group, the SLE group had significantly higher plasma/serum PRL levels (P 0.001), with the SMD of 1.26 and 95%CI (0.70，1.82). Subgroup analyses showed that SLE patients from Asia and Europe had higher plasma/serum PRL levels. However, no significant change in plasma/serum PRL levels was observed in SLE patients from America (P 0.05).Overall, our study suggests that SLE patients have higher plasma/serum PRL level, but with a regional difference.

The difference in the pharmacokinetics of schizandrin (SZ) in male and female rats was studied. SZ concentrations in the plasma were determined after the intragastric (i.g) administration of 10 mg/kg and the intravenous (i.v) administration of 5 mg/kg in male and female rats, respectively. It was found that the plasma concentrations of SZ in female rats were significantly higher than those in male rats. Drug absolute bioavailability, based on the area under curve (AUC(0-tn)), in female rats was roughly 20 times of that in male rats. The terminate half-life (T(1/2)) in male rats was shorter than that in female rats. These results demonstrate the existence of marked gender differences for SZ in rats.

CGRP is reported to be implicated in the process of diabetes and neuronal disease. However, the role and underlying mechanism of CGRP involved in diabetic neuropathy is unknown. Schwann cells play a central role in diabetic neuropathy, therefore the protective effect of CGRP on Schwann cells exposed to high glucose is determined. In the present study, full-length CGRP cDNA was isolated and then transferred to gateway adapted lentivirus expression vector by LR recombination reaction. Afterwards, the CGRP bearing recombinant virus was prepared in 293 FT cells and used to infect Schwann cells. The viability and superoxide anions of Schwann cells were evaluated following stimulation with high glucose, and levels of SOD, MDA and NOX1 were assessed. The results suggested that CGRP expression was up-regulated following lentivirus transfection. Lenti-CGRP increased cell viability in high glucose, but the effect was transient. Further lenti-CGRP protected against oxidative stress in Schwann cells triggered by high glucose and lenti-CGRP was effective in increasing SOD and decreasing MDA level. Meanwhile, the increased level of NOX1 caused by high glucose was reversed by lenti-CGRP overexpression. We therefore, suggest that lenti-CGRP may play a role in inhibiting oxidative stress in Schwann cell lines following hyperglycemic stimulation.

Thymoquinone (TQ) is the primary bioactive component of Nigella sativa Linn seed oil and used as anti-inflammatory, anti-oxidant, and anti-neoplastic agent. Previous studies have shown that TQ exhibits inhibitory effects on multiple cancers. However, the detailed antineoplastic effects and its molecular mechanisms of TQ on lung cancer are not entirely elucidated yet. In the present study, we aimed to investigate the effects of TQ on cell proliferation, migration, and invasion as well as its underlying anti-metastatic mechanisms in A549 cells. Lung cancer cell line A549 cells were treated with different concentration of TQ for different period of time, and the growth-inhibitory effects of TQ was measured by MTT and cell count assays; cell cycle was determined by flow cytometry; wound healing and transwell assays were used to assess the cell migration and invasion activities; Western blot and real-time quantitative RT-PCR were used to determine the expression of proliferation and invasion associated genes as well as MAPKs pathway molecules; gelatinase activity was estimated using gelatin zymography assay. The results show that TQ played a role in inhibiting the proliferation, migration, and invasion of A549 lung cancer cells, it also inhibited the expression level of PCNA, cyclin D1, MMP2, and MMP9 mRNA and protein in a dose- and time-dependent manner especially at 10, 20, 40 μmol/L concentrations. The cell cycle inhibitor P16 expression and the gelatinase activities of MMP2 and MMP9 were also inhibited by TQ dramatically. TQ reduced phosphorylation of ERK1/2; however, the proliferation and invasion inhibitory effects of TQ on A549 cells were neutralized by ERK1/2 inhibitor PD98059. In conclusion, our study confirmed that TQ could inhibit A549 cell proliferation, migration, and invasion through ERK1/2 pathway, as proposed the therapeutic potential of TQ as an anti-metastatic agent in human lung cancer treatment.

Differential pressure vacuum casting process exist some characteristics, such as nonlinear, time-varying, lag and so on, which is a dynamic process with parameter changing. In the casting process, in order to make parameters meet requirements, the compression model of casting system must be analyzed correspondingly. Pressure time formula of compression process is derived by means of vacuum technology theory, and V450N-VD Vacuum Casting Machine designed by Shanghai University is used to do experiments and its results show that the cross-sectional area of inlet valve and the initial pressure of vacuum chamber are the important parameters of affecting pressure time during compression process. With the motorcycle headlight shell as the experimental mold during the vacuum casting process, experiments show that reasonable pressure time is beneficial to improving the casting quality during the compression process.

Purpose To select the most powerful predictors for the evaluation of hepatic steatosis grade. Methods and materials Forty-five healthy New Zealand rabbits were randomly divided into one normal control group and three experimental groups. Hepatic steatosis models were established by feeding a high-fat, high-sugar diet and drinking water containing 5% ethanol. Twenty-two variable indexes were measured using general observation, biochemical examination, ultrasonography, computed tomography (CT), and proton magnetic resonance spectroscopy (MRS). Univariate analysis, correlation analysis, and stepwise regression analysis were used to make the selection of the most powerful predictors. ROC analysis was used to compare the diagnostic efficacy of single index with combined index ( Y ) expressed by a regression equation. Results Based on statistical analysis, there were 12 variable indexes with significant differences among groups, which correlated with hepatic steatosis grade: liver weight, hepatic index, liver CT value, liver-to-muscle attenuation ratio, 1 H MRS fat peak value, fat peak area, fat-to-water peak area ratio, fat percentage, ultrasound attenuation coefficient, serum aspartate aminotransferase, total cholesterol (TC) and triglycerides. Among them hepatic index, liver CT value and serum TC were selected as the most powerful predictors for hepatic steatosis grade with correlation coefficients of 0.709, −0.764, and 0.886, respectively. The regression equation was: Y = 1.975 + 3.906 × 10 −2 X 1 + 0.369 X 2 − 2.84 × 10 −2 X 3 , where Y = hepatic steatosis grade, X 1 = TC, X 2 = hepatic index, and X 3 = liver CT value. ROC analysis displayed PPV, NPV, curve area of combined index ( Y ) were superior to simple index (hepatic index, liver CT value and serum TC) in evaluating hepatic steatosis grade, and they were nearly 1.0000, 1.0000 and 1.000, respectively. Conclusions Combined application of several diagnostic methods is superior to simple diagnostic method, and could provide comprehensive, rapid, accurate evaluation of hepatic steatosis grade.

Objective To investigate the level of plasma adiponectin (APN) in atrial fibrillation (AF) patients and clinical value. Methods 1. 40 AF patients hospitalised in cardiology department in our hospital divided into two groups of paroxysmal and persistent (containing persistent and permanent AF) according AF guideline of ACC/AHA 2006. Control group comprised 15 patients admitted to hospital in Cardiology Department without AF. Plasma adiponectin level were measured and compared among the three groups. 2. All the patients fasting periphery venous flood acquired on the second morning, fasting plasma glucose (FPG), triglyeride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), creatinine (Cre) are tested by auto-biochemistry instrument, enzyme linked immunosorbent assay adopted. 3. Two-dimensional and Doppler echocardiography was performed using a Vivid 7 Dimension echo machine. Left ventricle end-diastolic diameter (LVEDD) and left atrial (LA) dimensions were standard M-mode measurements. Left ventricle ejection fraction (LVEF) was calculated using the modified Simpson9s rule. 4. After centrifugation, 0.5 ml clear supernatant liquid of fasting periphery venous flood deserved in −80°C less than 5 months. APN concentration was measured by radio-immunity method. 5. Record each general state, including BMI, medicine taking, whether with or without hypertension, coronary heart disease and so on. All data are expressed as mean±SD. All analyses were performed using SPSS 17.0. Results Adiponectin concentration in persistent AF was significantly higher than in control group and paroxymal group. Covariance analysis revealed that plasma adiponectin was also significantly associated with the presence of arterial fibrillation (p Conclusion High plasma adiponectin levels are associated with the presence of persistent and permanent AF. Adiponectin concentration was correlated negatively with TG.

Objective To explore the level of plasma visfatin in patients with coronary artery disease (CAD) and different BMI, and evaluate the relationship between plasma visfatin and coronary lesion severity in obese patients with CAD. Methods 59 causes were undergone coronary angiography and divided into three sub-groups: normal weight (13 causes) (BMI 2 ), over weight (31 causes) (24≤BMI 2 ) and obese groups (15 causes) (BMI≥28 kg/m 2 ). The levels of plasma visfatin of CAD group and control group were measured and compared. The correlation between plasma visfatin and coronary lesion severity score with different BMI was analysed. Result The plasma visfatin level was higher in the CAD group (547.21±94.18 ng/ml) comparing with the control group (470.86±87.99 ng/ml). In obese patients with CAD the plasma visfatin level (586.62±96.77 ng/ml) increased more significantly and it was positively correlated with Gensini score (p Conclusion The level of plasma visfatin is closely correlated with coronary lesion severity in obese patients with CAD. It might be used as a new clinical marker to predict the severity of coronary lesion in obese patients with CAD.

Objective To detect the N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure, and to evaluate the difference of the levels in patients with chronic left and right heart failure. Methods 1. 83 patients with chronic heart failure as the experimental group, and 25 patients without organic heart disease as the control group were included in the study. The patients in the experimental group were divided into left heart failure group (31 cases), right heart failure group (25 cases) and total cardiac failure group (27 cases), in which 25 patients of right heart failure group had chronic cor pulmonale, and the left heart failure and total cardiac failure group included 31 cases of coronary heart disease, 15 cases of hypertensive heart disease, 12 cases of heart valve disease. In the left heart failure and total cardiac failure group, the patients were further divided into three subgroups according to the classification of the New York Heart Academy (NYHA), including 17, 22 and 19 patients in Class II, III and IV, respectively; 2. Collected peripheral vein blood from each patient, and assayed the plasma NT-proBNP, creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) by ELISA; 3. Evaluated the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), right ventricular end diastolic diameter (RVEDD) and ventricular septal thickness (IVST) of these patients by echocardiography; 4. SPSS11.5 was used for statistical analysis, statistical significance was established at p Results 1. The level of plasma NT-proBNP were 79.53±36.77 pg/ml, 2076.95±1024.32 pg/ml, 743.26±152.82 pg/ml and 4815.52±3165.98 pg/ml in the control group, the left heart failure group, the right heart failure group and the total cardiac failure group respectively (p 0.05); 4. The plasma NT-proBNP level was negatively correlated with LVEF (r=−0.425, p 0.05). Multivariate stepwise regression analysis demonstrated that the CRE and LVEF were the independent factors influencing the plasma NT-proBNP level. Conclusions 1. The plasma NT-proBNP level of the patients with chronic heart failure was higher than normal, and the plasma NT-proBNP levels were significantly increased with the severity of cardiac function classification, and it is good at reflecting the abnormal of cardiac function. The plasma NT-proBNP level of the left heart failure was significantly higher than the right heart failure. Furthermore detecting the plasma NT-proBNP levels can distinguish between cardiac dyspnoea and pulmonary dyspnoea; 2. The plasma NT-proBNP level of the total cardiac failure group was significantly higher than the other groups. The plasma NT-proBNP level is important to detect serious heart failure. The CRE of total cardiac failure group was higher than other groups. The highter CRE suggests that patients of serious heart failure are often accompanied with a decline of renal function; 3. The plasma NT-proBNP level was negatively correlated with the LVEF, and positively correlated with the BUN, CRE and LVEDD. The CRE and LVEF are independent impact factors effecting the plasma NT-proBNP level.