Circulating DNA is defined as a kind of extracellular DNA that exists in plasma,cerebrospinal fluid and synovial fluid.The concentration of circulating DNA of cancer patients is significantly higher than that in healthy people.The genetic and epigenetic alterations of circulating cell-free nucleic acids are relevant to cancer development and progression,for example,gene mutation,DNA methylation and microsatellite instability and so on.The quantitative and qualitative detection of circulating DNA shows promising potential value in cancer screening,diagnosis,disease monitoring treatment and prognosis.

Objective Both right and left ventricular function should be taken into account in the assessment of anthracycline (ATC)-induced cardiotoxicity.The aim of this study was to assess the subclinical dysfunction of right cardiac system in patients with newly diagnosed lymphoma who received ATC treatment by echocardiography.Methods A total of 74 patients with lymphoma who received ATC treatment were enrolled.Each patient underwent transthoracic echocardiographic examination before chemotherapy as well as after two,four and six cycles of ATC remedy.Right atrial (RA) and right ventricular (RV) end-diastolic area (EDA) and end-systolic area (ESA) were calculated.RV end-diastolic volume (EDV) and end-systolic volume (ESV),as well as RV ejection fraction (EF) were measured simultaneously.Tissue Doppler imaging (TDI) measurements of systolic and early or late diastolic myocardial velocities of RV free wall at tricuspid annuals were also analyzed.Two-dimensional speckle tracking echocardiography (2DSTE) was conducted to evaluate RV free wall strain along with strain rate.Results None of the echocardiographic parameters showed significant alteration after two and four cycles of chemotherapy compared with those at baseline (P＞0.05).At the end of the therapy (i.e.after six cycles of ATC treatment),there was still no statistical difference on TDI data aswell as 2DSTE measurements (P＞0.05).An unexpected finding was that the RAEDA((6.6±1.9) cm2 vs (7.7±2.4) cm2) and RAESA ((8.8±2.5) cm2 vs (10.8±2.8) cm2) revealed obvious dilatation after six cures of the regimen compared with those at baseline (P＜0.01).Similar morphologic characteristics displayed on the RVEDA ((14.1 ±3.4) cm2 vs (16.2±3.7) cm2) and RVESA ((7.9±1.9) cm2 vs (9.0±2.2) cm2) (P＜0.01)simultaneously.Furthermore,RVEDV ((29.8±10.5) ml vs (37.0±12.7) ml) and RVESV ((12.7±4.4) ml vs (15.0±5.2) ml),as well as RVEF ((59.4±5.8)％ vs (56.4±5.8)％),in patients with lymphoma presented statistically significant difference between basic state and the level after six cycles of chemotherapy (P＜0.01).Meanwhile,no marked change was detected on left ventricular ejection fraction(LVEF) throughout the follow-up period (P＞0.05).Conclusions Echocardiography can be used easily and noninvasively to assess right cardiac system subclinical dysfunction.ATC-induced cardiotoxicity of right cardiac system is firstly manifested as morphological changes than the measurements with novel echocardiographic techniques.In addition,RVEF expresses as a valuable parameter for assessing subtle RV impaired performance in patients with lymphoma received ATC therapy.

Objective To investigate the value of echocardiographic Tei index combined with serum high-sensitivity cardiac troponin T(hs-cTnT) on monitoring cardiac toxicity associated with anthracycline chemotherapy drug in patients with diffuse large B-cell lymphoma(DLBCL).Methods PW-Tei index,TDI-Tei index of left/right ventricles and radionuclide cardiac measurement were acquired from 56 patients with DLBCL before,after the completion of 2-4 cycle(100-200 mg/m2) and 6-8 cycle(300-400 mg/m2) of the regimen,part of them received serum hs-cTnT detection at the same time.Cardiac toxicity event was defined as a relative reduction of radionuclide left ventricular ejection fraction(LVEF) of ≥10％ during the regime or an absolute radionuclide LVEF≤50％ after the complete chemotherapy.Results Compared with baseline,left ventricular PW-Tei index significantly increased after whole cures [(0.36-± 0.12) vs (0.44 ±0.13) vs (0.40 ± 0.13),P =0.002].After complete regimen,serum hs-cTnT level elevated significantly [(0.006 ± 0.006)tg/L vs (0.012 ± 0.007) μg/L vs (0.020±0.013)tμg/L,P =0.001].The sensitivity,specificity and area under ROC curve of early diagnosis of anthracycline-induced cardiotoxicity with elevated serum hs-cTnT in 2-4 cycle and increased left ventricular PW-Tei index in 6-8cycle detected together were 75％,85％,0.736 and 92％,50％,0.675,respectively(all P ＜0.05).Conclusions Echocardiographic PW-Tei index combined with serum hs-cTnT is a simple method and can be easily obtained in outpatient settings to monitor early cardiac toxicity induced by anthracycline therapy.

Objective To evaluate the subclinical dysfunction of left ventricle (LV) induced by anthracycline(ATC) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) by two-dimensional speckle tracking echocardiography (2DSTE) as well as real-time three-dimensional echocardiography (RT3DE).Methods Traditional echocardiography images and RT3DE images were acquired from 59 patients with DLBCL before,after the completion of two cures(100 mg∕m 2)and four cures of the regimen(200 mg∕m 2).LV global longitudinal strain(GLS),global circumferential strain(GCS),LV apical rotation and basal rotation,LV end-diastolic volume (EDV),end-systolic volume (ESV),stroke volume(SV) and ejection fraction(EF)were calculated simultaneously.Results Compared with baseline, LV apical rotation and basal rotation reduced significantly after two cures and four cures of therapy [LV apical rotation:(5.34±1 .80)°vs (3.80±1 .45)°vs (2.96±1 .1 8)°;LV basal rotation:(-3.32±1 .14)°vs (-2.65±1 .12)°vs (-2.56±1 .19)°;both P <0.01].LV GLS and GCS decreased significantly till four cures of treatment compared with those at baseline[GLS:(-21 .62±2.5 1)% vs(-20.1 7±2.74)%;GCS:(-26.34±4.76)% vs (-23.27 ±4.73)%;both P <0.01].The alternation on EDV,ESV,SV and EF manifested no visible degradation during the whole procedure (P > 0.05 for all). Conclusions Cardiotoxicity during the early phase of anthracycline treatment can be detected via 2DSTE prior to the traditional echocardiographic expression of ventricular systolic function.The left ventricular rotation index seems to be more sensitive than strain parameters for the estimation of early cardiac injury in patients with ATC chemotherapy.There is no safe dose for anthracycline in all patients with DLBCL treated with anthracycline even at lower doses.

Objective Rheumatoid arthritis (RA) is a systemic autoimmune disease, which mainly involves joints across the body, resulting in joint stiffness and loss of daily activity. Recent evidence suggests that numerous self-reacting T cells, including Th1 and Th17, infiltrate the synovium in RA patients, accompanied by functionally-compromised Treg. Iguratimod, a new small molecule with anti-inflammatory and immunomodulatory effects, has shown curative effects in animal models of arthritis. In this study, we aimed to test the clinical effects of Iguratimodˊs on RA patients and its role in immunoregulation. Methods We examined the clinical effects of iguratimod on RA patients in a random controlled clinical trials and analyzed its effects on Th1, Th17 and Treg as well as their associated cytokines and transcription factors by flow cytometry and real-time polymerase chain reaction (PCR). Then t-test, chi-square test and rank sum test were used to conduct statistical analysis. Results Our results revealed that iguratimod therapy provided significantly greater clinical benefit [ACR20, ACR50, ACR70 reached 50%, 20%, 15% respectively in iguratimod treatment group, Z=-2.216,P=0.027] than placebo group with the reduction of Th1 and Th17 but increment of Treg after iguratimod treatment [Th1: week 0 (26.5 ±8.0)%, week 24 (14.2 ±7.3)%, P<0.01; Th17:week 0 (1.7±0.7)%, week 24 (1.3±0.4)%, P<0.05;Treg:week 0 (6.8±1.6)%, week 24 (8.9±2.9)%, P<0.05], which was statistically significant. Conclusion Our results provide theoretical and clinical based evidence for the impact of iguratimod on immunomodulation of RA.

Objective:To explore the protective effect of the water-soluble total flavonoids from Isodon lophanthoides var.gerardia-nus (Benth.) H.Hara on LO2 cells damage.Methods:The cytotoxicity was evaluated by MTT cell viability determination to confirm the concentration range .Hepatocyte damage model was established by H 2 O2 treatment.After the oxidative stress hepatocyte was coin-cubated with WSTF at different concentrations for various times , the protective effect of WSTF on H 2 O2-induced hepatocyte damage was evaluated by MTT cell viability determination and the content determination of ALT , AST and MDA in cell supernatant .The inhibition of WSTF against H 2 O2-induced LO2 cells apoptosis was evaluated by the quantitative determination of Rhodamine 123 fluorescence and intracellular ROS.Results:The LO2 cells injured by 0.3 mmol· L-1 H2 O2 treatment for 4 h were used as the hepatocyte damage model.The concentration range of WSTF was 0.0312-0.125 mg· ml-1.WSTF could inhibit H2O2-induced injury in LO2 cells and obviously reduce ALT, AST and MDA.Moreover, WSTF could reverse mitochondrial membrane potential depolarization and decrease the amount of intracellular ROS .Conclusion:WSTF exhibits notable protective and curative effects on hepatocyte damage in vitro.

Objective:The therapeutic effect of less polar ginsenosides on rats with rheumatoid arthritis was studied, and the metabolic pathway that produce anti-inflammatory effect of less polar ginsenosides was identified.Methods:Rats were randomly divided into the control group, the model group, methotrexate treatment group, and high dose, medium dose, and low dose less polar ginsenosides groups. After 30 days of oral administration, less polar ginsenosides reduced the disease activity significantly in rats with rheumatoid arthritis. Blood and ankle synovial tissue metabolisms were measured by ultra performance liquid chromatography (UPLC) tandem mass spectrometry (MS) to explore the mechanism of less polar ginsenosides.The resulting data were subjected to principal component analysis and orthogonal partial least squares discriminant analysis(OPLS-DA).Results:Compared with the model group, erythrocyte sedimentation rate and RF decreased significantly in the high dose of less polar ginsenosides ( P<0.01). Metabolomics showed that R2X and R2Y of serum OPLS-DA were 0.626 and 0.904 respectively. The R2X and R2Y of synovial OPLS-DA were 0.429 and 0.689 respectively. Major differential metabolites were identified in the model group of rats, including arachidonic acid, valine, linoleic acid, and guanine nucleoside, etc. The main differential metabolites were identified in rats in the high dose group of less polar ginsenosides, including linoleic acid, betaine, eicosapentaenoic acid, alanine, methionine sulfoxide, isoleucine, etc. Conclusion:The metabolic spectrum has shown that inflammation is associated with linoleic acid metabolism, valine, leucine and isoleucine degradation, arachidonic acid metabolism. Less polar ginsenosides regulatethe linolenic acid metabolism, methionine metabolism and glucose alanine cycle.

Here, we took base construction of neurosurgery as example to discuss and analyze according to requirements and evaluation indexes of base construction in Xinqiao Hospital, and put forward the specific objectives, measures and implementations of base construction. Foremost, we summarized experiences and overcame shortcomings through interpreting and implementing scheme of our base construction, which would help to improve the construction of standardized residency training base in China.

Objective:To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats.Methods:Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1β, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group.Results:Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased ( P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1β [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased ( P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased ( P<0.01), serum FSH, IL-1β and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion:RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.

Porcine circovirus type 2(PCV2)mainly damages the immune cells of pigs,causing lym-phocyte depletion and immune suppression.Interleukin(IL)-15 regulates immune functions wide-ly,and plays an important regulatory role in the survival,proliferation,differentiation and immune function of a variety of immune cells such as natural killer(NK),CD8+T cells and NKT cells.In this study,in order to determine the effect of PCV2 on IL-15 expression,4-week-old piglets(n=4)were infected with PCV2 and the negative control group(n=4)was set up.On day 7 post-infec-tion,the inguinal lymph nodes of the infected and control groups were collected,and porcine cyto-kine antibody microarray(QAP-CYT-1)was employed to quantify the expression of cytokines in the tissues,screen for differential cytokines,and GO and KEGG enrichment analysis for IL-15 were conducted.Real-time quantitative fluorescent PCR(qPCR)and ELISA were used to verify the level of IL-15 mRNA and protein,and those in porcine peripheral blood mononuclear cells(PBMC)and serum were simultaneously detected.Compared with the negative control group,the expression lev-el of IL-15 was significantly reduced in the infected group(P＜0.05);IL-15 was mainly involved in cytokine-cytokine receptor interactions,immune responses,cellular activation,and the regulation of JAK-STAT and TNF signaling pathways.The levels of IL-15 mRNA and protein in inguinal lymph nodes in the infected group were significantly lower than those in the control group(P＜0.05),which was consistent with the detection results of QAP-CYT-1.However,there was no significant difference in IL-15 mRNA and protein levels in PBMC and serum.These results indicate that PCV2 can inhibit IL-15 in the inguinal lymph node microenvironment of piglets.This study can provide important information for further revealing the immunosuppressive mechanism of PCV2.